Displaying publications 1 - 20 of 48 in total

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  1. Chan Y, Ng SW, Mehta M, Gupta G, Chellappan DK, Dua K
    Future Med Chem, 2020 11;12(21):1887-1890.
    PMID: 33054387 DOI: 10.4155/fmc-2020-0206
    Matched MeSH terms: Tuberculosis/drug therapy
  2. Laghari M, Talpur BA, Syed Sulaiman SA, Khan AH, Bhatti Z
    Int J Mycobacteriol, 2020 8 31;9(3):281-288.
    PMID: 32862161 DOI: 10.4103/ijmy.ijmy_75_20
    Background: The frequency, severity, and the nature of anti-tuberculosis (TB)-induced adverse drug reactions (ADRs) have always been the matter of concern. The present study was, therefore, aimed to study the incidence, risk factors, and effect of anti-tuberculosis treatment (ATT) among TB children.

    Methods: A prospective longitudinal study was conducted in the Sindh province, Pakistan. A total of 508 TB children in multicenter hospitals under ATT were assessed for ADRs. Naranjo Causality Assessment and Hartwig's Severity Assessment Scale were used.

    Results: A total of 105 ADRs were reported in 67 (13.2%) of 508 patients. Gastrointestinal disorders were the most frequently observed ADRs (65.7%), followed by arthralgia (24.8%). Around 65 (61.9%) of ADRs were identified as probable and 78 (74.3%) as mild severe ADRs during the study. A total of four cases of mild hepatotoxicity were observed among children. On multivariate analysis, the independent variables which had statistically significant positive association with ADRs were female (OR; 2.66, P = 0.004), retreatment (OR; 22.32, P = ≤ 0.001), and absence of BCG scar (OR; 17.84, P = 0.001).

    Conclusions: The finding of the current study suggests that close monitoring of females, patients with previous TB treatment, and those without BCG is warranted at the study site.

    Matched MeSH terms: Tuberculosis/drug therapy*
  3. Goroh MMD, Rajahram GS, Avoi R, Van Den Boogaard CHA, William T, Ralph AP, et al.
    Infect Dis Poverty, 2020 Aug 26;9(1):119.
    PMID: 32843089 DOI: 10.1186/s40249-020-00739-7
    BACKGROUND: Tuberculosis (TB) is of high public health importance in Malaysia. Sabah State, located on the island of Borneo, has previously reported a particularly high burden of disease and faces unique contextual challenges compared with peninsular Malaysia. The aim of this study is to describe the epidemiology of TB in Sabah to identify risk groups and hotspots of TB transmission.

    METHODS: We conducted a retrospective review of TB cases notified in Sabah, Malaysia, between 2012 and 2018. Using data from the state's 'myTB' notification database, we calculated the case notification rate and described trends in the epidemiology, diagnostic practices and treatment outcomes of TB in Sabah within this period. The Chi-squared test was used for determining the difference between two proportions.

    RESULTS: Between 2012 and 2018 there were 33 193 cases of TB reported in Sabah (128 cases per 100 000 population). We identified several geographic hotspots, including districts with > 200 cases per 100 000 population per year. TB rates increased with age and were highest in older males. Children drug resistant (MDR) TB prevalence was low (0.3% of TB cases), however, rapid diagnostic test coverage was low (1.2%) and only 18% of all cases had a positive culture result. Treatment success was 83% (range: 81-85%) in those with drug-sensitive TB and 36% (range: 25-45%) in cases of MDR-TB.

    CONCLUSION: Between 2012 and 2018, TB notifications in Sabah State equated to 20% of Malaysia's total TB notifications, despite Sabah representing only 10% of Malaysia's population. We found hotspots of TB in urbanised population hubs and points of migration, as well as evidence of late presentation and diagnosis. Ensuring universal health coverage and expansion of GeneXpert® coverage is recommended to reduce barriers to care and early diagnosis and treatment for TB.

    Matched MeSH terms: Tuberculosis/drug therapy
  4. González Fernández L, Casas EC, Singh S, Churchyard GJ, Brigden G, Gotuzzo E, et al.
    J Int AIDS Soc, 2020 Jan;23(1):e25438.
    PMID: 31913556 DOI: 10.1002/jia2.25438
    INTRODUCTION: Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally.

    DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary.

    CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.

    Matched MeSH terms: Tuberculosis/drug therapy
  5. Tok PSK, Liew SM, Wong LP, Razali A, Loganathan T, Chinna K, et al.
    PLoS One, 2020;15(4):e0231986.
    PMID: 32320443 DOI: 10.1371/journal.pone.0231986
    INTRODUCTION: The monitoring of tuberculosis (TB) treatment outcomes and examination of the factors affecting these outcomes are important for evaluation and feedback of the national TB control program. This study aims to assess the TB treatment outcomes among patients registered in the national TB surveillance database in Malaysia from 2014 until 2017 and identify factors associated with unsuccessful treatment outcomes and all-cause mortality.

    MATERIALS AND METHODS: Using registry-based secondary data, a retrospective cohort study was conducted. TB patients' sociodemographic characteristics, clinical disease data and treatment outcomes at one-year surveillance were extracted from the database and analyzed. Logistic regression analysis was used to determine factors associated with unsuccessful treatment outcomes and all-cause mortality.

    RESULTS: A total of 97,505 TB cases (64.3% males) were included in this study. TB treatment success (cases categorized as cured and completed treatment) was observed in 80.7% of the patients. Among the 19.3% patients with unsuccessful treatment outcomes, 10.2% died, 5.3% were lost to follow-up, 3.6% had outcomes not evaluated while the remaining failed treatment. Unsuccessful TB treatment outcomes were found to be associated with older age, males, foreign nationality, urban dwellers, lower education levels, passive detection of TB cases, absence of bacille Calmette-Guerin (BCG) scar, underlying diabetes mellitus, smoking, extrapulmonary TB, history of previous TB treatment, advanced chest radiography findings and human immunodeficiency virus (HIV) infection. Factors found associated with all-cause mortality were similar except for nationality (higher among Malaysians) and place of residence (higher among rural dwellers), while smoking and history of previous TB treatment were not found to be associated with all-cause mortality.

    CONCLUSIONS: This study identified various sociodemographic characteristics and TB disease-related variables which were associated with unsuccessful TB treatment outcomes and mortality; these can be used to guide measures for risk assessment and stratification of TB patients in future.

    Matched MeSH terms: Tuberculosis/drug therapy*
  6. Paton NI, Borand L, Benedicto J, Kyi MM, Mahmud AM, Norazmi MN, et al.
    Int J Infect Dis, 2019 Oct;87:21-29.
    PMID: 31301458 DOI: 10.1016/j.ijid.2019.07.004
    Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO 'End TB' targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI.
    Matched MeSH terms: Latent Tuberculosis/drug therapy*
  7. Khan AH, Sulaiman SAS, Laghari M, Hassali MA, Muttalif AR, Bhatti Z, et al.
    BMC Infect Dis, 2019 Aug 05;19(1):691.
    PMID: 31382889 DOI: 10.1186/s12879-019-4312-9
    BACKGROUND: Extra-pulmonary tuberculosis (EPTB) represents about 14% of all cases of tuberculosis (TB) in Malaysia. The aims of the study include evaluation of socio-demographic factors, clinical manifestations, co-morbidities among patients with EPTB and their treatment outcomes.

    METHODS: A retrospective study was conducted to recognize the epidemiology facts of EPTB. Individual data for EPTB patients were collected from TB registers, laboratory TB registers, treatment cards and TB medical personal files into a standardized study questionnaire. Crude (COR) and adjusted odds ratios (AOR) and 95% confidence intervals (CI) were determined to assess the risk factors for EPTB and unsuccessful treatment outcomes.

    RESULTS: There were 1222 EPTB patients presenting 13.1% of all TB cases during 2006-2008. Pleural effusion and lymph node TB were the most frequent types and accounted for 45.1% of all EPTB cases among study participants. Treatment success rate was 67.6%. The best treatment completion rates were found in children ≤15 years (0.478 [0.231-1.028]; p = 0.05). On multivariate analysis, age group 56-65 years (1.658 [1.157-2.376]; p = 0.006), relapse cases (7.078 [1.585-31.613]; p = 0.010), EPTB-DM (1.773 [1.165-2.698]; p = 0.008), patients with no formal (2.266 [1.254-4.095]; p = 0.001) and secondary level of education (1.889 [1.085-3.288]; p = 0.025) were recorded as statistically positive significant risk factors for unsuccessful treatment outcomes. Patients at the risk of EPTB were more likely to be females (1.524 [1.311-1.746]; p 

    Matched MeSH terms: Tuberculosis/drug therapy*
  8. Mazlun MH, Sabran SF, Mohamed M, Abu Bakar MF, Abdullah Z
    Molecules, 2019 Jul 04;24(13).
    PMID: 31277371 DOI: 10.3390/molecules24132449
    Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) remains one of the deadliest, infectious diseases worldwide. The detrimental effects caused by the existing anti-TB drugs to TB patients and the emergence of resistance strains of M. tuberculosis has driven efforts from natural products researchers around the globe in discovering novel anti-TB drugs that are more efficacious and with less side effects. There were eleven main review publications that focused on natural products with anti-TB potentials. However, none of them specifically emphasized antimycobacterial phenolic compounds. Thus, the current review's main objective is to highlight and summarize phenolic compounds found active against mycobacteria from 2000 to 2017. Based on the past studies in the electronic databases, the present review also focuses on several test organisms used in TB researches and their different distinct properties, a few types of in vitro TB bioassay and comparison between their strengths and drawbacks, different methods of extraction, fractionation and isolation, ways of characterizing and identifying isolated compounds and the mechanism of actions of anti-TB phenolic compounds as reported in the literature.
    Matched MeSH terms: Tuberculosis/drug therapy*
  9. Akkerman O, Aleksa A, Alffenaar JW, Al-Marzouqi NH, Arias-Guillén M, Belilovski E, et al.
    Int J Infect Dis, 2019 Jun;83:72-76.
    PMID: 30953827 DOI: 10.1016/j.ijid.2019.03.036
    The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.
    Matched MeSH terms: Tuberculosis/drug therapy
  10. Chin KL, Sarmiento ME, Norazmi MN, Acosta A
    Tuberculosis (Edinb), 2018 12;113:139-152.
    PMID: 30514496 DOI: 10.1016/j.tube.2018.09.008
    Tuberculosis (TB), caused by Mycobacterium tuberculosis complex (MTBC), is an infectious disease with more than 10.4 million cases and 1.7 million deaths reported worldwide in 2016. The classical methods for detection and differentiation of mycobacteria are: acid-fast microscopy (Ziehl-Neelsen staining), culture, and biochemical methods. However, the microbial phenotypic characterization is time-consuming and laborious. Thus, fast, easy, and sensitive nucleic acid amplification tests (NAATs) have been developed based on specific DNA markers, which are commercially available for TB diagnosis. Despite these developments, the disease remains uncontrollable. The identification and differentiation among MTBC members with the use of NAATs remains challenging due, among other factors, to the high degree of homology within the members and mutations, which hinders the identification of specific target sequences in the genome with potential impact in the diagnosis and treatment outcomes. In silico methods provide predictive identification of many new target genes/fragments/regions that can specifically be used to identify species/strains, which have not been fully explored. This review focused on DNA markers useful for MTBC detection, species identification and antibiotic resistance determination. The use of DNA targets with new technological approaches will help to develop NAATs applicable to all levels of the health system, mainly in low resource areas, which urgently need customized methods to their specific conditions.
    Matched MeSH terms: Tuberculosis/drug therapy
  11. AlMatar M, Makky EA, Var I, Kayar B, Köksal F
    Pharmacol Rep, 2018 Apr;70(2):217-226.
    PMID: 29475004 DOI: 10.1016/j.pharep.2017.09.001
    Tuberculosis (TB) is described as lethal disease in the world. Resistant to TB drugs is the main reason to have unfavourable outcomes in the treatment of TB. Therefore, new agents to replace existing drugs are urgently needed. Previous reports suggested that InhA inhibitors, an enoyl-ACP-reductase, might provide auspicious candidates which can be developed into novel antitubercular agents. In this review, we explain the role of InhA in the resistance of isoniazid. Furthermore, five classes of InhA inhibitors, which display novel binding modes and deliver evidence of their prosperous target engagement, have been debated.
    Matched MeSH terms: Tuberculosis/drug therapy*
  12. AlMatar M, Makky EA, Yakıcı G, Var I, Kayar B, Köksal F
    Pharmacol Res, 2018 02;128:288-305.
    PMID: 29079429 DOI: 10.1016/j.phrs.2017.10.011
    Tuberculosis (TB) presently accounts for high global mortality and morbidity rates, despite the introduction four decades ago of the affordable and efficient four-drugs (isoniazid, rifampicin, pyrazinamide and ethambutol). Thus, a strong need exists for new drugs with special structures and uncommon modes of action to effectively overcome M. tuberculosis. Within this scope, antimicrobial peptides (AMPs), which are small, cationic and amphipathic peptides that comprise a section of the innate immune system, are currently the leading potential agents for the treatment of TB. Many studies have recently illustrated the capability of anti-mycobacterial peptides to disrupt the normal mycobacterial cell wall function through various modes, thereby interacting with the intracellular targets, as well as encompassing nucleic acids, enzymes and organelles. This review presents a wide array of antimicrobial activities, alongside the associated properties of the AMPs that could be utilized as potential agents in therapeutic tactics for TB treatment.
    Matched MeSH terms: Tuberculosis/drug therapy*
  13. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    J Gastroenterol Hepatol, 2018 Jan;33(1):30-36.
    PMID: 29024102 DOI: 10.1111/jgh.14018
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
    Matched MeSH terms: Tuberculosis/drug therapy*
  14. Singh G, Kesharwani P, Srivastava AK
    Curr Drug Deliv, 2018;15(3):312-320.
    PMID: 29165080 DOI: 10.2174/1567201814666171120125916
    BACKGROUND: Tuberculosis is an infection and caused by gentle growing bacteria. The Internet provides opportunities for people with tuberculosis (TB) to connect with one another to address these challenges.

    OBJECTIVE: The aim of this paper is to introduce readers to the platforms on which Tuberculosis participants interact, to discuss reasons for and risks associated with TB-related activity, and to review research related to the potential impact of individual participation on TB outcomes.

    METHODS: Research and online content related to Tuberculosis online activity is reviewed, however, the difficulty in accurate prescribing and adhering to these protocols and the emergence of M. tuberculosis strains resistant to multiple drugs and drug-drug interactions that interfere with optimal treatment of Tuberculosis and co-infected patients with the different disease has generated a pressing need for improved Tuberculosis therapies.

    RESULTS: Together with the ominous global burden of Tuberculosis, those shortcomings of current medication have contributed to a renewed interest in the development of improved drugs and protocols for the medication of Tuberculosis. This article features obstacles related with the enhanced utilization of existing drugs and difficulties related with the advancement of enhanced products, concentrating on perspectives characteristic in Tuberculosis drug clinical improvement. The participation includes peer support, advocacy, self-expression, seeking and sharing TB information, improving approaches to Tuberculosis data management, and humour.

    CONCLUSION: This article highlights hurdles related to the optimised use of existing drugs and challenges related to the development of improved products, focusing on aspects inherent in Tuberculosis drug clinical development. Concluding comments offer processes for more efficient development of Tuberculosis therapies and increase the quality of life.

    Matched MeSH terms: Tuberculosis/drug therapy*
  15. Hakkimane SS, Shenoy VP, Gaonkar SL, Bairy I, Guru BR
    Int J Nanomedicine, 2018;13:4303-4318.
    PMID: 30087562 DOI: 10.2147/IJN.S163925
    INTRODUCTION: Tuberculosis (TB) is the single largest infectious disease which requires a prolonged treatment regime with multiple drugs. The present treatment for TB includes frequent administration of a combination of four drugs for a duration of 6 months. This leads to patient's noncompliance, in addition to developing drug-resistant strains which makes treatment more difficult. The formulation of drugs with biodegradable polymeric nanoparticles (NPs) promises to overcome this problem.

    MATERIALS AND METHODS: In this study, we focus on two important drugs used for TB treatment - rifampicin (RIF) and isoniazid (INH) - and report a detailed study of RIF-loaded poly lactic-co-glycolic acid (PLGA) NPs and INH modified as INH benz-hydrazone (IH2) which gives the same therapeutic effect as INH but is more stable and enhances the drug loading in PLGA NPs by 15-fold compared to INH. The optimized formulation was characterized using particle size analyzer, scanning electron microscopy and transmission electron microscopy. The drug release from NPs and stability of drug were tested in different pH conditions.

    RESULTS: It was found that RIF and IH2 loaded in NPs release in a slow and sustained manner over a period of 1 month and they are more stable in NPs formulation compared to the free form. RIF- and IH2-loaded NPs were tested for antimicrobial susceptibility against Mycobacterium tuberculosis H37Rv strain. RIF loaded in PLGA NPs consistently inhibited the growth at 70% of the minimum inhibitory concentration (MIC) of pure RIF (MIC level 1 µg/mL), and pure IH2 and IH2-loaded NPs showed inhibition at MIC equivalent to the MIC of INH (0.1 µg/mL).

    CONCLUSION: These results show that NP formulations will improve the efficacy of drug delivery for TB treatment.

    Matched MeSH terms: Tuberculosis/drug therapy
  16. Danjuma L, Ling MP, Hamat RA, Higuchi A, Alarfaj AA, Marlina, et al.
    Tuberculosis (Edinb), 2017 12;107:38-47.
    PMID: 29050770 DOI: 10.1016/j.tube.2017.03.006
    Mycobacterium tuberculosis has a remarkable ability of long-term persistence despite vigorous host immunity and prolonged therapy. The bacteria persist in secure niches such as the mesenchymal stem cells in the bone marrow and reactivate the disease, leading to therapeutic failure. Many bacterial cells can remain latent within a diseased tissue so that their genetic material can be incorporated into the genetic material of the host tissue. This incorporated genetic material reproduces in a manner similar to that of cellular DNA. After the cell division, the incorporated gene is reproduced normally and distributed proportionately between the two progeny. This inherent adoption of long-term persistence and incorporating the bacterial genetic material into that of the host tissue remains and is considered imperative for microbial advancement and chemotherapeutic resistance; moreover, new evidence indicates that the bacteria might pass on genetic material to the host DNA sequence. Several studies focused on the survival mechanism of M. tuberculosis in the host immune system with the aim of helping the efforts to discover new drugs and vaccines against tuberculosis. This review explored the mechanisms through which this bacterium affects the expression of human genes. The first part of the review summarizes the current knowledge about the interactions between microbes and host microenvironment, with special reference to the M. tuberculosis neglected persistence in immune cells and stem cells. Then, we focused on how bacteria can affect human genes and their expression. Furthermore, we analyzed the literature base on the process of cell death during tuberculosis infection, giving particular emphasis to gene methylation as an inherited process in the neutralization of possibly injurious gene components in the genome. The final section discusses recent advances related to the M. tuberculosis interaction with host epigenetic circuitry.
    Matched MeSH terms: Latent Tuberculosis/drug therapy
  17. Shah K, Chan LW, Wong TW
    Drug Deliv, 2017 Nov;24(1):1631-1647.
    PMID: 29063794 DOI: 10.1080/10717544.2017.1384298
    The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.
    Matched MeSH terms: Tuberculosis/drug therapy*
  18. Schüz J, Fored M
    Methods Inf Med, 2017 Aug 11;56(4):328-329.
    PMID: 28726979 DOI: 10.3414/ME17-14-0004
    BACKGROUND: This accompanying editorial is an introduction to the focus theme of "chronic disease registries - trends and challenges".

    METHODS: A call for papers was announced on the website of Methods of Information in Medicine in April 2016 with submission deadline in September 2016. A peer review process was established to select the papers for the focus theme, managed by two guest editors.

    RESULTS: Three papers were selected to be included in the focus theme. Topics range from contributions to patient care through implementation of clinical decision support functionality in clinical registries; analysing similar-purposed acute coronary syndrome registries of two countries and their registry-to-SNOMED CT maps; and data extraction for speciality population registries from electronic health record data rather than manual abstraction.

    CONCLUSIONS: The focus theme gives insight into new developments related to disease registration. This applies to technical challenges such as data linkage and data as well as data structure abstraction, but also the utilisation for clinical decision making.

    Matched MeSH terms: Tuberculosis/drug therapy
  19. Javaid A, Hasan R, Zafar A, Chaudry MA, Qayyum S, Qadeer E, et al.
    Int J Tuberc Lung Dis, 2017 03 01;21(3):303-308.
    PMID: 28225340 DOI: 10.5588/ijtld.16.0444
    BACKGROUND: Drug resistance in general, and multidrug-resistant tuberculosis (MDR-TB) in particular, threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Pakistan.

    OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Pakistan.

    METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in all provinces of Pakistan. We performed culture and drug susceptibility testing on M. tuberculosis isolates from patients with a prior history of anti-tuberculosis treatment (retreatment cases) from all over the country.

    RESULTS: Of 544 isolates from previously treated cases, 289 (53.1%) were susceptible to all first-line drugs, 255 (46.9%) were resistant to at least one anti-tuberculosis drug and 132 (24.3%) were MDR-TB. Among MDR-TB isolates, 47.0% were ofloxacin (OFX) resistant. Extensively drug-resistant TB was found in two (0.4%) isolates.

    CONCLUSION: Prevalence of drug resistance in retreatment isolates was high. The alarmingly high prevalence of OFX resistance among MDR-TB isolates may threaten the success of efforts to control and treat MDR-TB.

    Matched MeSH terms: Extensively Drug-Resistant Tuberculosis/drug therapy*
  20. Parumasivam T, Ashhurst AS, Nagalingam G, Britton WJ, Chan HK
    Mol Pharm, 2017 01 03;14(1):328-335.
    PMID: 27977216 DOI: 10.1021/acs.molpharmaceut.6b00905
    Rifapentine is an anti-tuberculosis (anti-TB) drug with a prolonged half-life, but oral delivery results in low concentrations in the lungs because of its high binding (98%) to plasma proteins. We have shown that inhalation of crystalline rifapentine overcomes the limitations of oral delivery by significantly enhancing and prolonging the drug concentration in the lungs. The delivery of crystalline particles to the lungs may promote inflammation. This in vivo study characterizes the inflammatory response caused by pulmonary deposition of the rifapentine particles. The rifapentine powder was delivered to BALB/c mice by intratracheal insufflation at a dose of 20 mg/kg. The inflammatory response in the lungs and bronchoalveolar lavage (BAL) was examined at 12 h, 24 h, and 7 days post-treatment by flow cytometry and histopathology. At 12 and 24 h post-treatment, there was a significant influx of neutrophils into the lungs, and this returned to normal by day 7. A significant recruitment of macrophages occurred in the BAL at 24 h. Consistent with these findings, histopathological analysis demonstrated pulmonary vascular congestion and significant macrophage recruitment at 12 and 24 h post-treatment. In conclusion, the pulmonary delivery of crystalline rifapentine caused a transient neutrophil-associated inflammatory response in the lungs that resolved over 7 days. This observation may limit pulmonary delivery of rifapentine to once a week at a dose of 20 mg/kg or less. The effectiveness of weekly dosing with inhalable rifapentine will be assessed in murine Mycobacterium tuberculosis infection.
    Matched MeSH terms: Tuberculosis/drug therapy
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