Comparison of Interferon-γ Release Assay to Two Cut-Off Points of Tuberculin Skin Test to Detect Latent Mycobacterium tuberculosis Infection in Primary Health Care Workers

Background

An interferon-γ release assay, QuantiFERON-TB (QFT) test, has been introduced an alternative test for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Here, we compared the performance of QFT with tuberculin skin test (TST) measured at two different cut-off points among primary health care work (HCW) in Brazil.

Methods

A cross-sectional study was carried out among HCWs in four Brazilian cities with a known history of high incidence of TB. Results of the QFT were compared to TST results based on both ≥5 mm and ≥10 mm as cut-off points.

Results

We enrolled 632 HCWs. When the cut-off value of ≥10 mm was used, agreement between QFT and TST was 69% (k = 0.31), and when the cut-off of ≥5 mm was chosen, the agreement was 57% (k = 0.22). We investigated possible factors of discordance of TST vs QFT. Compared to the TST−/QFT− group, risk factors for discordance in the TST+/QFT− group with TST cut-off of ≥5 mm included age between 41–45 years [OR = 2.70; CI 95%: 1.32–5.51] and 46–64 years [OR = 2.04; CI 95%: 1.05–3.93], BCG scar [OR = 2.72; CI 95%: 1.40–5.25], and having worked only in primary health care [OR = 2.30; CI 95%: 1.09–4.86]. On the other hand, for the cut-off of ≥10 mm, BCG scar [OR = 2.26; CI 95%: 1.03–4.91], being a household contact of a TB patient [OR = 1.72; CI 95%: 1.01–2.92] and having had a previous TST [OR = 1.66; CI 95%: 1.05–2.62], were significantly associated with the TST+/QFT− group. No statistically significant associations were found among the TST−/QFT+ discordant group with either TST cut-off value.

Conclusions

Although we identified BCG vaccination to contribute to the discordance at both TST cut-off measures, the current Brazilian recommendation for the initiation of LTBI treatment, based on information gathered from medical history, TST, chest radiograph and physical examination, should not be changed.     

Comparison of the Tuberculin Skin Test and Interferon Gamma Release Assay for the Screening of Tuberculosis in Adolescents in Close Contact with Tuberculosis TB Patients

Background

The tuberculin skin test (TST) frequently yields false positive results among BCG-vaccinated persons thereby limiting its diagnostic value particularly in settings with high BCG vaccination rate. We determined the agreement between IGRA and TST using 2 cutoff values and identified possible relationships between the results of these tests and the development of active tuberculosis.

Methodology

Adolescents aged 11–19 years in close contact with smear-positive tuberculosis cases and with normal chest radiographs were recruited from middle and high schools in South Korea. The TST was conducted by trained nurses, and blood was drawn for the QuantiFERON-TB Gold In-Tube (QFT-GIT). Participants were followed up for 2 years to check for incidence tuberculosis.

Results

A total of 2,982 subjects were included in the study, the average age was 15.1 years (SD 1.3), 61% had BCG vaccination scars. The agreement of QFT-GIT and the TST was low (κ = 0.38, 95% CI 0.32 to 0.42) using 10 mm cutoff; however, when the 15 mm cutoff was used, the agreement was intermediate (κ = 0.56, 95% CI 0.50 to 0.61). The odds ratio (OR) for the development of active tuberculosis was 7.9 (95% CI 3.46 to 18.06) for QFT-GIT positive patients, 7.96 (95% CI 3.14-20.22) for TST/QFT-GIT+ and the OR 4.62 (95% CI 2.02 to 10.58) and 16.35 (95% CI 7.09 to 37.71) for TST 10 mm and 15 mm cutoff respectively.

Conclusions

The results of this study suggest that the TST cutoff point for patients aged 11–17 years would be 15 mm in other study. The OR of QFT-GIT for the development of active tuberculosis and its intermediate agreement with TST using 15 mm cutoff demonstrates its role as an adjunct diagnostic tool to current clinical practice. Positive responders to both TST and QFT-GIT at the outset may benefit from chemoprophylaxis.     

Strategy to Better Select HIV-Infected Individuals for Latent TB Treatment in BCG-Vaccinated Population

Objective

To evaluate the T-SPOT.TB interferon-γ releasing assay and the tuberculin skin test (TST), for the diagnosis of latent tuberculosis infection(LTBI) and the development of subsequent active tuberculosis, in BCG-vaccinated HIV-infected individuals.

Methods

HIV-infected individuals without clinical suspicion of active TB or a past history of TB were enrolled from 1 January 2008 to 30 November 2010. Both T-SPOT.TB test and TST were offered to the participants whom were followed up prospectively until April 30, 2012 for development of TB.

Results

Among the 909 participants, 25% had positive TST reactions with cut-off point of 5 mm and 15% had positive T-SPOT.TB results. After a median follow-up of 2.97 years, there were 5 cases developed culture-confirmed active TB (all had dual positive TST and T-SPOT.TB results), and the incidence was 0.17 per 100 person-years. The relative risks (RRs) for subsequent active TB in HIV-infected individuals with positive TST results, positive T-SPOT.TB results and dual positive results compared with the risk for individuals with negative results were 40.6 (95% CI 2.1–767.9), 73.9 (95% CI 3.9–1397.7) and 226.5 (95% CI 12.0–4284), respectively. The number needed to treat to prevent one subsequent TB case among patients with a positive TST, a positive T-SPOT.TB and dual positive results was 35, 22 and 8 respectively.

Conclusions

Adopting positive results of the TST and T-SPOT.TB to screen LTBI among BCG-vaccinated HIV-infected individuals might be feasible. Number needed to treat for isoniazid preventive therapy could be reduced significantly by using dual positive strategy.     

Prevalence and Incidence of Latent Tuberculosis Infection in Georgian Healthcare Workers

Background

Tuberculosis is a major occupational hazard in low and middle-income countries. Limited data exist on serial testing of healthcare workers (HCWs) with interferon-γ release assays (IGRAs) for latent tuberculosis infection (LTBI), especially in low and middle-income countries. We sought to evaluate the rates of and risk factors for LTBI prevalence and LTBI test conversion among HCWs using the tuberculin skin test (TST) and QuantiFERON-TB Gold In-tube assay (QFT-GIT).

Methods

A prospective longitudinal study was conducted among HCWs in the country of Georgia. Subjects completed a questionnaire, and TST and QFT-GIT tests were performed. LTBI testing was repeated 6-26 months after baseline testing.

Results

Among 319 HCWs enrolled, 89% reported prior BCG vaccination, and 60% worked in TB healthcare facilities (HCFs). HCWs from TB HCFs had higher prevalence of positive QFT-GIT and TST than those from non-TB HCFs: 107/194 (55%) vs. 30/125 (31%) QFT-GIT positive (p<0.0001) and 128/189 (69%) vs. 64/119 (54%) TST positive (p = 0.01). There was fair agreement between TST and QFT-GIT (kappa = 0.42, 95% CI 0.31–0.52). In multivariate analysis, frequent contact with TB patients was associated with increased risk of positive QFT-GIT (aOR 3.04, 95% CI 1.79–5.14) but not positive TST. Increasing age was associated with increased risk of positive QFT-GIT (aOR 1.05, 95% CI 1.01–1.09) and TST (aOR 1.05, 95% CI 1.01–1.10). High rates of HCW conversion were seen: the QFT-GIT conversion rate was 22.8/100 person-years, and TST conversion rate was 17.1/100 person-years. In multivariate analysis, female HCWs had decreased risk of TST conversion (aOR 0.05, 95% CI 0.01–0.43), and older HCWs had increased risk of QFT-GIT conversion (aOR 1.07 per year, 95% CI 1.01–1.13).

Conclusion

LTBI prevalence and LTBI test conversion rates were high among Georgian HCWs, especially among those working at TB HCFs. These data highlight the need for increased implementation of TB infection control measures.     

Increase in the Number of Tuberculosis Cases Treated following Tuberculin Skin Testing in First-Year Schoolchildren in Madagascar

Background

Tuberculosis continues to cause unacceptably high levels of disease and death worldwide. Active preventive strategies are required to improve tuberculosis control and to increase the number of cases treated in developing countries. The aim of this study was to evaluate the utility of the tuberculin skin test (TST) in first-year schoolchildren as a means of increasing the number of tuberculosis cases detected through the screening of close contacts.

Methods

All members of the households of 90 schoolchildren assigned to three groups on the basis of TST category (≤5 mm, [5–15)mm, ≥15 mm) were screened for sputum smear-positive pulmonary tuberculosis. The percentage detection of tuberculosis in close contacts was compared between TST categories.

Results

We identified 433 close contacts of the 90 schoolchildren, who were then evaluated for tuberculosis. We identified 11 cases of pulmonary tuberculosis among the close contacts (7 already on treatment and 4 previously undiagnosed): 0 in TST category ≤5 mm, 3 in TST category [5–15) mm and 8 in TST category ≥15 mm). This approach increased the detection of tuberculosis cases by a factor of 1.6 in first-year schoolchildren of the TST ≥5 mm group.

Conclusion

TST in first-year schoolchildren is a potentially effective method for improving the detection of tuberculosis in close contacts.     

Tuberculin Skin Test Result and Risk of Death among Persons with Active TB

Background

Although the tuberculin skin test (TST) is frequently used to aid in the diagnosis of tuberculosis (TB) disease and to identify persons with latent TB infection, it is an imperfect test and approximately 10–25% of persons with microbiologically confirmed TB disease have a negative TST. Previous studies have suggested that persons with a negative TST are more likely to present with severe TB disease and have an increased rate of TB-related death.

Methods

We analyzed culture-confirmed TB cases captured in US TB surveillance data from 1993 to 2008 and performed multivariate logistic regression analysis to determine the association between TST result and death.

Results

Of 284,866 cases of TB reported in the US, 58,180 persons were eligible for inclusion in the analysis and 3,270 of those persons died after initiating TB treatment. Persons with a negative TST accounted for only 14% of the eligible cases but accounted for 42% of the deaths. Persons with a TST≥15 mm had 67% lower odds of death than persons with a negative TST (adjusted odds ratio 0.33, 95% confidence interval 0.30–0.36).

Conclusions

A negative TST is associated with an increased risk of death among persons with culture-confirmed TB disease, even after adjustment for HIV status, site of TB disease, sputum smear AFB status, drug susceptibility, age, sex, and origin of birth. In addition to indicating risk of developing disease, the TST may also be a marker for increased risk of death.     

Prevalence of Latent and Active Tuberculosis among Dairy Farm Workers Exposed to Cattle Infected by Mycobacterium bovis

Background

Human tuberculosis caused by M. bovis is a zoonosis presently considered sporadic in developed countries, but remains a poorly studied problem in low and middle resource countries. The disease in humans is mainly attributed to unpasteurized dairy products consumption. However, transmission due to exposure of humans to infected animals has been also recognized. The prevalence of tuberculosis infection and associated risk factors have been insufficiently characterized among dairy farm workers (DFW) exposed in settings with poor control of bovine tuberculosis.

Methodology/Principal Findings

Tuberculin skin test (TST) and Interferon-gamma release assay (IGRA) were administered to 311 dairy farm and abattoir workers and their household contacts linked to a dairy production and livestock facility in Mexico. Sputa of individuals with respiratory symptoms and samples from routine cattle necropsies were cultured for M. bovis and resulting spoligotypes were compared. The overall prevalence of latent tuberculosis infection (LTBI) was 76.2% (95% CI, 71.4–80.9%) by TST and 58.5% (95% CI, 53.0–64.0%) by IGRA. Occupational exposure was associated to TST (OR 2.72; 95% CI, 1.31–5.64) and IGRA (OR 2.38; 95% CI, 1.31–4.30) adjusting for relevant variables. Two subjects were diagnosed with pulmonary tuberculosis, both caused by M. bovis. In one case, the spoligotype was identical to a strain isolated from bovines.

Conclusions

We documented a high prevalence of latent and pulmonary TB among workers exposed to cattle infected with M. bovis, and increased risk among those occupationally exposed in non-ventilated spaces. Interspecies transmission is frequent and represents an occupational hazard in this setting.     

Tuberculin Skin Test Distribution following a Change in BCG Vaccination Policy

Background

Epidemiologic data regarding tuberculin skin test (TST) responses are an important basis for TB control strategies. This study analyzed TST responses in Korea, which experienced a rapid change in BCG vaccination status.

Methods

TST responses in young adults were examined over 5 years. Participants with active TB lesions were excluded.

Results

A total of 5,552 participants were enrolled with median age of 21 years. When an induration diameter ≥10 mm was used as the criterion for a positive test, TST positivity fell (from 28.0% in 2005 to 15.3% in 2009); however, they remained steady when the criterion was ≥15–20 mm. A positive TST was associated with a personal or family of TB, the presence of a Bacille Calmette-Guérin (BCG) scar, and age (odds ratio [95% confidence interval] = 4.03 [2.61–6.22], 2.91 [1.80–4.71], 1.50 [1.31–1.72], and 1.15 [1.09–1.20], respectively). Among these factors, the decrease of participants with BCG scars was the most prominent change, which appeared to be associated with the change of TST positivity rate.

Conclusion

Overall, the rate of TST positivity in Korea decreased. However, this trend seems associated with the change of BCG vaccination strategy rather than successful control of LTBI. This study showed that change in BCG vaccination strategy can have great impact on TB epidemiologic survey based on TST.     

Risk factors associated with positive QuantiFERON-TB Gold In-Tube and tuberculin skin tests results in Zambia and South Africa

Introduction

The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis.

Objectives

To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST.

Methods

Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors.

Results

A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06–1.25, and for TST aOR: 1.10; 95% CI 1.01–1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39–0.67) and TST (aOR: 0.61; 95% CI: 0.46–0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90–1.74) and TST (aOR: 1.39; 95% CI: 0.98–1.98) results. We found little evidence in our data to support our hypotheses.

Conclusion

QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST.     

Active Case Finding of Tuberculosis (TB) in an Emergency Room in a Region with High Prevalence of TB in Brazil

Setting

Public hospital emergency room (ER) in Porto Alegre, Brazil, a setting with high prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV) infection.

Objective

To determine the prevalence of PTB, using a symptom based active case finding (ACF) strategy in the ER of a public hospital in an area with high prevalence of TB and HIV, as well as variables associated with pulmonary TB diagnosis.

Methods

Cross sectional study. All patients ≥18 years seeking care at the ER were screened for respiratory symptoms and those with cough ≥2 weeks were invited to provide a chest radiograph and two unsupervised samples of sputum for acid-fast bacilli smear and culture.

Results

Among 31,267 admissions, 6,273 (20.1%) reported respiratory symptoms; 197 reported cough ≥2 weeks, of which pulmonary TB was diagnosed in 30. In multivariate analysis, the variables associated with a pulmonary tuberculosis diagnosis were: age (OR 0.94, 95% CI: 0.92–0.97; p<0.0001), sputum production (OR 0.18, 95% CI 0.06–0.56; p = 0.003), and radiographic findings typical of TB (OR 12.11, 95% CI 4.45–32.93; p<0.0001).

Conclusions

This study identified a high prevalence of pulmonary TB among patients who sought care at the emergency department of a tertiary hospital, emphasizing the importance of regular screening of all comers for active TB in this setting.     

Comparing Interferon-Gamma Release Assays to Tuberculin Skin Test in Thai Children with Tuberculosis Exposure

Background

Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure.

Methods

This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT.

Results

158 children were enrolled (87% TB-exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV infection. 66.7% had TST≥10 mm, while 38.6% had TST≥15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42–46% for TST≥10 mm and 62–67% for TST≥15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T-Spot.TB.

Conclusions

Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings.     

Assessing the Quality of Tuberculosis Evaluation for Children with Prolonged Cough Presenting to Routine Community Health Care Settings in Rural Uganda

Background

Improving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse.

Objective

To describe the current practices and quality of TB evaluation for children with cough ≥2 weeks'' duration presenting to community health centers in Uganda.

Methods

Cross-sectional analysis of children (<15 years) receiving care at five Level IV community health centers in rural Uganda for any reason between 2009–2012. Quality of TB care was assessed using indicators derived from the International Standards of Tuberculosis Care (ISTC).

Results

From 2009–2012, 1713 of 187,601 (0.9%, 95% CI: 0.4–1.4%) children presenting to community health centers had cough ≥ 2 weeks'' duration. Of those children, only 299 (17.5%, 95% CI: 15.7–19.3%) were referred for sputum microscopy, but 251 (84%, 95% CI: 79.8–88.1%) completed sputum examination if referred. The yield of sputum microscopy was only 3.6% (95% CI: 1.3–5.9%), and only 55.6% (95% CI: 21.2–86.3%) of children with acid-fast bacilli positive sputum were started on treatment. Children under age 5 were less likely to be referred for sputum examination and to receive care in accordance with ISTC. The proportion of children evaluated in accordance with ISTC increased over time (4.6% in 2009 to 27.9% in 2012, p = 0.03), though this did not result in increased case-detection.

Conclusion

The quality of TB evaluation was poor for children with cough ≥2 weeks'' duration presenting for health care. Referrals for sputum smear microscopy and linkage to TB treatment were key gaps in the TB evaluation process, especially for children under the age of five.     

Coffee Consumption and Risk of Fracture in the Cohort of Swedish Men (COSM)

Background

Recent research in a large cohort of women showed that coffee consumption is not associated with increased risk of fracture. Whether this is the case also among men is less clear.

Methods

In the Cohort of Swedish Men (COSM) study, 42,978 men aged 45–79 years old at baseline in 1997 answered a self-administered food frequency questionnaire covering coffee consumption and a medical and lifestyle questionnaire covering potential confounders. Our main outcomes first fracture at any site and first hip fracture were collected from the National Patient Registry in Sweden. The association between coffee consumption and fracture risk was investigated using Cox’s proportional hazards regression.

Results

During a mean follow-up of 11.2 years, 5,066 men had a first fracture at any site and of these, 1,186 (23%) were hip fractures. There was no association between increasing coffee consumption (per 200 ml) and rate of any fracture (hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.99–1.02) or hip fracture (HR 1.02; 95% CI 0.99–1.06) after adjustment for potential confounders. For men consuming ≥4 cups of coffee/day compared to those consuming <1 cup of coffee/day, HR for any type of fracture was 0.91 (95% CI 0.80–1.02) and for hip fracture: 0.89 (95% CI 0.70–1.14).

Conclusions

High coffee consumption was not associated with an increased risk of fractures in this large cohort of Swedish men.     

Patterns of Anti-Osteoporosis Medication Use among Women at High Risk of Fracture: Findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

Objective

To assess patterns of anti-osteoporosis medication (AOM) use over 3 years among women at high risk of major fracture.

Methods

The GLOW registry follows a cohort of more than 40,000 women aged ≥55 from 615 primary care practices in 10 countries. Self-administered surveys (baseline, 12, 24, and 36 months) collected data on patient characteristics, perception of fracture risk, and AOM use. FRAX scores were calculated from the baseline surveys and women classified as high risk if their FRAX 10-year probability of major fracture was ≥20%.

Results

A total of 5774 women were classified as at high risk and had complete data over 3 years. At baseline, 2271 (39%) reported receiving AOM, 739 (13%) reported prior but not current use, and 2764 (48%) said they had never used AOM. Over 3 years, 85% of baseline non-users continued as non-users and 15% initiated AOM; among baseline users, 49% continued the same medication class, 29% stopped AOM, and 12% switched. Women who stopped AOM were less likely to self-report osteoporosis (HR 0.56, 95% CI 0.42–0.75) than women who continued AOM. Compared with non-users who did not begin treatment, women initiating AOM were more likely to report a diagnosis of osteoporosis (HR 11.3, 95% CI 8.2–15.5) or osteopenia (HR 4.1, 95% CI 2.9–5.7) and be very concerned about osteoporosis (HR 1.9, 95% CI 1.3–2.8).

Conclusions

Less than 40% of women at high risk of fracture reported taking AOM. Women who stopped AOM were less likely to believe they have osteoporosis. Women who initiated treatment appeared motivated primarily by a diagnosis of osteoporosis or osteopenia and concern about the condition.     

Risk of Psychiatric Disorders following Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study

Background

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A higher prevalence of psychiatric comorbidities, including depressive disorder, anxiety disorder, and bipolar disorder has been proved in patients with PCOS. However, a clear temporal causal relationship between PCOS and psychiatric disorders has not been well established.

Objective

We explored the relationship between PCOS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder.

Methods

We identified patients who were diagnosed with PCOS by an obstetrician-gynecologist in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without PCOS who were matched according to age and sex. The occurrence of subsequent new-onset psychiatric disorders was evaluated in both cohorts based on diagnoses made by psychiatrists.

Results

The PCOS cohort consisted of 5431 patients, and the comparison cohort consisted of 21,724 matched control patients without PCOS. The incidence of depressive disorder (hazard ratio [HR] 1.296, 95% confidence interval [CI] 1.084–.550), anxiety disorder (HR 1.392, 95% CI 1.121–1.729), and sleep disorder (HR 1.495, 95% CI 1.176–1.899) were higher among the PCOS patients than among the patients in the comparison cohort. In addition, a higher incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0–1, 1–5, ≥5 y).

Conclusions

PCOS might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder. The risk of newly diagnosed bipolar disorder, which has often been reported in the literature to be comorbid with PCOS, was not significantly elevated.     

TB Screening in Canadian Health Care Workers Using Interferon-Gamma Release Assays

Background

While many North American healthcare institutions are switching from Tuberculin Skin Test (TST) to Interferon-gamma release assays (IGRAs), there is relatively limited data on association between occupational tuberculosis (TB) risk factors and test positivity and/or patterns of test discordance.

Methods

We recruited a cohort of Canadian health care workers (HCWs) in Montreal, and performed both TST and QuantiFERON-TB Gold In Tube (QFT) tests, and assessed risk factors and occupational exposure.

Results

In a cross-sectional analysis of baseline results, the prevalence of TST positivity using the 10 mm cut-off was 5.7% (22/388, 95%CI: 3.6–8.5%), while QFT positivity was 6.2% (24/388, 95%CI: 4–9.1%). Overall agreement between the tests was poor (kappa = 0.26), and 8.3% of HCWs had discordant test results, most frequently TST−/QFT+ (17/388, 4.4%). TST positivity was associated with total years worked in health care, non-occupational exposure to TB and BCG vaccination received after infancy or on multiple occasions. QFT positivity was associated with having worked as a HCW in a foreign country.

Conclusions

Our results suggest that LTBI prevalence as measured by either the TST or the QFT is low in this HCW population. Of concern is the high frequency of unexplainable test discordance, namely: TST−/QFT+ subjects, and the lack of any association between QFT positivity and clear-cut recent TB exposure. If these discordant results are indeed false positives, the use of QFT in lieu of TST in low TB incidence settings could result in overtreatment of uninfected individuals.     

Red and Processed Meat Intake Is Associated with Higher Gastric Cancer Risk: A Meta-Analysis of Epidemiological Observational Studies

Background

Red and processed meat was concluded as a limited-suggestive risk factor of gastric cancer by the World Cancer Research Fund. However, recent epidemiological studies have yielded inconclusive results.

Methods

We searched Medline, EMBASE, and the Cochrane Library from their inception to April 2013 for both cohort and case-control studies which assessed the association between red and/or processed meat intake and gastric cancer risk. Study-specific relative risk estimates were polled by random-effect or fixed-effect models.

Results

Twelve cohort and thirty case-control studies were included in the meta-analysis. Significant associations were found between both red (RR: 1.45, 95% CI: 1.22–1.73) and processed (RR: 1.45, 95% CI: 1.26–1.65) meat intake and gastric cancer risk generally. Positive findings were also existed in the items of beef (RR: 1.28, 95% CI: 1.04–1.57), bacon (RR: 1.37, 95% CI: 1.17–1.61), ham (RR: 1.44, 95% CI: 1.00–2.06), and sausage (RR: 1.33, 95% CI: 1.16–1.52). When conducted by study design, the association was significant in case-control studies (RR: 1.63, 95% CI: 1.33–1.99) but not in cohort studies (RR: 1.02, 95% CI: 0.90–1.17) for red meat. Increased relative risks were seen in high-quality, adenocarcinoma, cardia and European-population studies for red meat. And most subgroup analysis confirmed the significant association between processed meat intake and gastric cancer risk.

Conclusions

Our findings indicate that consumption of red and/or processed meat contributes to increased gastric cancer risk. However, further investigation is needed to confirm the association, especially for red meat.     

Statins and Hip Fracture Prevention – A Population Based Cohort Study in Women

Objective

To study the association of long-term statin use and the risk of low-energy hip fractures in middle-aged and elderly women.

Design

A register-based cohort study.

Setting

Finland.

Participants

Women aged 45–75 years initiating statin therapy between 1996 and 2001 with adherence to statins ≥80% during the subsequent five years (n = 40 254), a respective cohort initiating hypertension drugs (n = 41 610), and women randomly selected from the population (n = 62 585).

Main Outcome Measures

Incidence rate of and hazard ratio (HR) for low-energy hip fracture during the follow-up extending up to 7 years after the 5-year exposure period.

Results

Altogether 199 low-energy hip fractures occurred during the 135 330 person-years (py) of follow-up in the statin cohort, giving an incidence rate of 1.5 hip fractures per 1000 py. In the hypertension and the population cohorts, the rates were 2.0 per 1000 py (312 fractures per 157 090 py) and 1.0 per 1000 py (212 fractures per 216 329 py), respectively. Adjusting for a propensity score and individual variables strongly predicting the outcome, good adherence to statins for five years was associated with a 29% decreased risk (HR 0.71; 95% CI 0.58–0.86) of a low-energy hip fracture in comparison with adherent use of hypertension drugs. The association was of the same magnitude when comparing the statin users with the population cohort, the HR being 0.69 (0.55–0.87). When women with poor (<40%), moderate (40 to 80%), and good adherence (≥80%) to statins were compared to those with good adherence to hypertension drugs (≥80%) or to the population cohort, the protective effect associated with statin use attenuated with the decreasing level of adherence.

Conclusions

5-year exposure to statins is associated with a reduced risk of low-energy hip fracture in women aged 50–80 years without prior hospitalizations for fractures.     

Risk Factors for Death in 632 Patients with Sickle Cell Disease in the United States and United Kingdom

Background

The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.

Methods and Results

We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67–75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV<3.0 m/sec (p<0.0001). The hazard ratios for death were 11.1 (95% CI 4.1–30.1; p<0.0001) for TRV≥3.0 m/sec, 4.6 (1.8–11.3; p = 0.001) for NT-proBNP≥160 pg/mL, and 14.9 (5.5–39.9; p<0.0001) for both TRV≥3.0 m/sec and NT-proBNP≥160 pg/mL. Age >47 years, male gender, chronic transfusions, WHO class III–IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.

Conclusions

A TRV≥3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable.

The study is registered in ClinicalTrials.gov with identifier

{"type":"clinical-trial","attrs":{"text":"NCT00492531","term_id":"NCT00492531"}}NCT00492531