Dataset Information

Extrapulmonary tuberculosis in Pakistan- A nation-wide multicenter retrospective study.

ABSTRACT: BACKGROUND:Pakistan is fifth among high burden countries for tuberculosis. A steady increase is seen in extrapulmonary tuberculosis (EPTB), which now accounts for 20% of all notified TB cases. There is very limited information on the epidemiology of EPTB. This study was performed with the aim to describe the demographic characteristics, clinical manifestations and treatment outcomes of EPTB patients in Pakistan. METHOD:We performed descriptive analysis on routinely collected data for cohorts of TB patients registered nationwide in 2016 at health facilities selected using stratified convenient sampling. FINDINGS:Altogether 54092 TB including 15790 (29.2%) EPTB cases were registered in 2016 at 50 study sites. The median age was 24 years for EPTB and 30 years for PTB patients. The crude prevalence of EPTB in females was 30.5% (95%CI; 29.9-31.0) compared to 27.9% (95%CI; 27.3-28.4) in males. The likelihood of having EPTB (OR), was 1.1 times greater for females, 2.0 times for children, and 3.3 times for residents of provinces in the North-West. The most common forms of EPTB were pleural (29.6%), lymphatic (22.7%) and abdominal TB (21.0%). Pleural TB was the most common clinical manifestation in adults (34.2%) and abdominal TB in children (38.4%). An increase in the prevalence of pleural and osteoarticular and decline in lymphatic and abdominal TB was observed with advancing age. Diversity in demography and clinical manifestations were noted between provinces. The treatment success rate for all type EPTB was significantly high compared to bacteriology confirmed PTB with the exception of EPTB affecting CNS with a high mortality rate. CONCLUSIONS:The study provides an insight into demography, clinical manifestations and treatment outcomes of EPTB. Further studies are needed to explain significant diversities observed between provinces, specific risk factors and challenges concerning EPTB management.

SUBMITTER: Tahseen S

PROVIDER: S-EPMC7188211 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Extrapulmonary tuberculosis in Pakistan- A nation-wide multicenter retrospective study.

Tahseen Sabira S Khanzada Faisal Masood FM Baloch Aurangzaib Quadir AQ Abbas Qasim Q Bhutto Mansoor Manzoor MM Alizai Ahmad Wali AW Zaman Shah S Qasim Zahida Z Durrani Muhammad Najeeb MN Farough M Khalid MK Ambreen Atiqa A Safdar Nauman N Mustafa Tehmina T

PloS one 20200428 4

<h4>Background</h4>Pakistan is fifth among high burden countries for tuberculosis. A steady increase is seen in extrapulmonary tuberculosis (EPTB), which now accounts for 20% of all notified TB cases. There is very limited information on the epidemiology of EPTB. This study was performed with the aim to describe the demographic characteristics, clinical manifestations and treatment outcomes of EPTB patients in Pakistan.<h4>Method</h4>We performed descriptive analysis on routinely collected data ...[more]

PMID: 32343714

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Project description:ObjectivesWe reported the incidence and associated factors of extrapulmonary tuberculosis (EPTB).DesignA retrospective cohort study.SettingBrunei Darussalam, an intermediate tuberculosis (TB)-burden country with stagnating annual TB rates.ParticipantsAll active TB cases identified in the country between January 2001 and December 2018 (18 years).Primary and secondary outcome measuresAnnual proportions of EPTB (overall and specific) were calculated. Multiple logistic regression was done to investigate factors associated with developing EPTB, when compared with pulmonary TB (PTB). Χ2 trend test was used to determine any trends during the 18-year study period.ResultsWe identified 3916 TB cases, among which 743 (19.0%) were EPTB cases. Lymphatic (44.8%) and pleural (19.4%) EPTB were most common. The main modes of diagnosis were tissue biopsy (73.6%) and radiological assessment (18.3%). Treatment success and mortality rate were 79.7% and 7.0%, respectively. Associations with specific EPTB types varies with age-group and gender. Younger age-group (adjusted OR (aOR)≥1.94) and women (aOR: 2.45 (95% CI: 1.94 to 3.11)) had higher adjusted odds of developing lymphatic EPTB, but had lower adjusted odds of developing pleural EPTB (younger age-group (aOR≤0.54) and women (aOR: 0.41 (95% CI: 0.17 to 0.90)). When compared to foreign residents, locals had higher adjusted odds of skeletal (aOR: 4.44 (95% CI: 2.04 to 11.69)), gastrointestinal (aOR: 3.91 (95% CI: 1.84 to 9.66)) and other types of EPTB (aOR: 3.42 (95% CI: 1.53 to 9.14)). No significant trend differences were observed for overall and specific EPTB types.ConclusionDespite being generally non-infectious and less recognised than PTB, understanding EPTB epidemiology is important as it also contributes to the overall TB burden in a country. Examining EPTB cases by their specific anatomical site would provide more information on risk factors. Raising public awareness on the EPTB symptoms and that TB affects lungs and other parts of the body could promote early health seeking behaviour and early EPTB diagnosis.

Project description:Approximately 5-10% of persons infected with M. tuberculosis develop tuberculosis, but the factors associated with disease progression are incompletely understood. Both linkage and association studies have identified human genetic variants associated with susceptibility to pulmonary tuberculosis, but few genetic studies have evaluated extrapulmonary disease. Because extrapulmonary and pulmonary tuberculosis likely have different underlying pathophysiology, identification of genetic mutations associated with extrapulmonary disease is important.We performed a pilot genome-wide association study among 24 persons with previous extrapulmonary tuberculosis and well-characterized immune defects; 24 pulmonary tuberculosis patients and 57 patients with M. tuberculosis infection served as controls. The Affymetrix GeneChip Human Mapping Xba Array was used for genotyping; after careful quality control, genotypes at 44,175 single nucleotide polymorphisms (SNPs) were available for analysis. Eigenstrat quantified population stratification within our sample; logistic regression, using results of the Eigenstrat analysis as a covariate, identified significant associations between groups. Permutation testing controlled the family-wise error rate for each comparison between groups. Four SNPs were significantly associated with extrapulmonary tuberculosis compared to controls with M. tuberculosis infection; one (rs4893980) in the gene PDE11A, one (rs10488286) in KCND2, and one (rs2026414) in PCDH15; one was in chromosome 7 but not associated with a known gene. Two additional variants were significantly associated with extrapulmonary tuberculosis compared with pulmonary tuberculosis; one (rs340708) in the gene FAM135B and one in chromosome 13 but not associated with a known gene. The function of all four genes affects cell signaling and activity, including in the brain.In this pilot study, we identified 6 novel variants not previously known to be associated with extrapulmonary tuberculosis, including two SNPs more common in persons with extrapulmonary than pulmonary tuberculosis. This provides some support for the hypothesis that the pathogenesis and genetic predisposition to extrapulmonary tuberculosis differs from pulmonary tuberculosis. Further study of these novel SNPs, and more well-powered genome-wide studies of extrapulmonary tuberculosis, is warranted.

Project description:Background: Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. However, a small proportion of pediatric patients develop a severe clinical condition, Multisystem Inflammatory Syndrome in Children (MIS-C). The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C. Methods: Peripheral blood samples were recruited from 43 confirmed MIS-C patients with a median age of 7.7 years, most of whom were of West-Eurasian origin. Four or more organ systems were involved in the majority of patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. Findings: The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts. The EPIMISC signature was also overrepresented in Kawasaki disease patients, a childhood pathology with also a possible viral trigger, that shares many of the clinical features of MIS-C. Interpretation: We have characterized DNA methylation loci that are associated with the onset of MIS-C. The identified genes are likely contributors to the characteristic exaggerated host inflammatory response observed in these patients. The described epigenetic signature could also provide new targets for more specific therapies for the disorder.

Project description:BackgroundClinical guidelines generally recommend endocrine therapy (ET) as first-line treatment of hormone receptor-positive advanced breast cancer (HR+ ABC) whereas chemotherapy (CT) should be considered in the presence of life-threatening disease or limited clinical benefit after three sequential ET regimens. However, it is unclear if real-world clinical practice is in accordance with the current guidelines. This study was to present the real-world treatment patterns and ET regimens among HR+ ABC patients in China.MethodsUsing data from the Nation-wide Multicenter Retrospective Clinical Epidemiology Study of Female Advanced Breast Cancer in China (ClinicalTrials.gov identifier: NCT03047889), we investigated the clinicopathological characteristics, clinical profiles, and treatment patterns of HR+ ABC patients from January 2012 to December 2014.ResultsA total of 2,342 patients with HR+ ABC were included in this study. Our findings revealed that, in comparisons with those receiving initial CT (n = 1445), patients initiated ET (n =402) were significantly older, later recurrent after adjuvant treatment, with a lower rate of visceral involvement and a decreasing quantity of metastatic sites. A total of 1,308 patients received palliative ET while only 18.9% patients (n = 247) reached three lines of ET. Among patients completing more than one line of ET, the median treatment duration was 8 months for the first line, 6 months for the second line, and 3 months for the third line for patients receiving ET. In the advanced setting, the choices of palliative ET regimens were diverse, yet aromatase inhibitor (AI) monotherapy was still the overall mainstay of ET; in contrast, patients were less accessible to everolimus plus AI regimen in this population.ConclusionsLess than one quarter of patients initiated palliative ET for HR+ ABC in routine clinical practice. Patients who received multi-lines of ET experienced successive shorter durations following each line of therapy. This real-life data provides a solid overview of ET for HR+ ABC from China, indicating unmet need for treatment options that improve the effectiveness of endocrine therapy.

Dataset Information

Extrapulmonary tuberculosis in Pakistan- A nation-wide multicenter retrospective study.

Publications

Extrapulmonary tuberculosis in Pakistan- A nation-wide multicenter retrospective study.

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