Tuberculosis Recurrence after Completion Treatment in a European City: Reinfection or Relapse?

Background

Tuberculosis (TB) recurrence can be due to reinfection or relapse. The contribution of each to TB incidence and the factors associated with recurrence are not well known. Effectiveness of TB control programs is assessed in part by recurrence rates. The aim of this study was to establish the recurrence rate of TB in Barcelona, the associated risk factors and the role of reinfection.

Methods

A population-based retrospective longitudinal study was performed in Barcelona, Spain. TB patients with positive culture results who completed treatment between Jan 1^st, 2003 and Dec 31^st, 2006 were followed-up until December 31st, 2009 by the TB Control Program. The incidence rate of recurrence was calculated per person-year of follow-up (py). Kaplan-Meier and Cox regression methods were used for the survival analysis by calculating the hazard ratio (HR) with 95% confidence intervals (CI).

Results

Of the 1,823 TB cases identified, 971 fulfilled the inclusion criteria and 13 (1.3%) had recurrent TB. The recurrence rate was 341 cases per 100,000 py, 13 times higher than the TB incidence of the general population. Likelihood of TB recurrence at the 1st, 3rd and 5th year of follow-up was 0.1%, 1.4% and 1.6%, respectively. Factors associated with recurrence were HIV infection (HR: 4.7, CI: 1.4–15.7), living in the inner city district (HR: 3.9, CI: 1.3–11.8) and history of TB treatment (HR: 5.2, CI: 1.7–16.2). Genotyping results of recurrent cases were available for 6 patients (3 reinfections and 3 relapses).

Conclusion

The rate of TB recurrence in Barcelona is low and most episodes occur within the first three years. Patients at higher risk of recurrence are co-infected with HIV, living in neighborhoods with high TB incidence or with a history of TB treatment. When available, genotyping results help determine whether the recurrence is due to reinfection or relapse.     

Risk of Active Tuberculosis in HIV-Infected Patients in Taiwan with Free Access to HIV Care and a Positive T-Spot.TB Test

BackgroundInterferon-gamma release assays (IGRAs) have been used to identify individuals at risk for developing active tuberculosis (TB). However, data regarding the risk of TB development in HIV-infected patients testing positive for IGRAs remain sparse in the era of combination antiretroviral therapy.MethodsBetween 2011 and 2013, 608 HIV-infected patients without active TB undergoing T-Spot.TB testing were enrolled in this prospective observational study at a university hospital designated for HIV care in Taiwan with a declining TB incidence from 72 per 100,000 population in 2005 to 53 per 100,000 population in 2012. All of the subjects were followed until September 30, 2014. The national TB registry was accessed to identify any TB cases among those lost to follow-up.ResultsT-Spot.TB tested negative in 534 patients (87.8%), positive in 64 patients (10.5%), and indeterminate in 10 patients (1.6%). In multivariate analysis, positive T-Spot.TB was significantly associated with older age (adjusted odds ratio [AOR], 1.172 per 10-year increase; 95% confidence interval [CI], 1.022-1.344, P=0.023), past history of TB (AOR, 13.412; 95% CI, 6.106-29.460, P<0.001), and higher CD4 counts at enrollment (AOR, per 50-cell/μl increase, 1.062; 95% CI, 1.017-1.109, P=0.007). Of the 64 patients testing positive for T-Spot.TB, none received isoniazid preventive therapy and all but 5 received combination antiretroviral therapy at the end of follow-up with the latest CD4 count and plasma HIV RNA load being 592.8 cells/μL and 1.85 log₁₀ copies/mL, respectively. One patient (1.6%) developed active TB after 167 person-years of follow-up (PYFU), resulting in an incidence rate of 0.599 per 100 PFYU. None of the 534 patients testing negative for T-Spot.TB developed TB after 1380 PYFU, nor did the 24 patients with old TB and positive T-Spot.TB tests develop TB after 62.33 PYFU.ConclusionsThe risk of developing active TB in HIV-infected patients with positive T-Spot.TB receiving combination antiretroviral therapy is low in Taiwan where the national TB program has led to a sustained decrease in TB incidence.     

Risk of a Second Primary Cancer after Non-melanoma Skin Cancer in White Men and Women: A Prospective Cohort Study

Background

Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC.

Methods and Findings

In two large US cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses'' Health Study (NHS), we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years). In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years). We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR = 1.11; 95% CI 1.05–1.18), and in women (RR = 1.20; 95% CI 1.15–1.25). Age-standardized absolute risk (AR) was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n = 28), in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR = 1.99, AR = 116 per 100,000 person-years). In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR = 1.19, AR = 87 per 100,000 person-years), lung (RR = 1.32, AR = 22 per 100,000 person-years), and melanoma (RR = 2.58, AR = 79 per 100,000 person-years).

Conclusion

This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women. Please see later in the article for the Editors'' Summary     

Mortality burden and socioeconomic status in India

Background

The dimensions along which mortality is patterned in India remains unclear. We examined the specific contribution of social castes, household income, assets, and monthly per capita consumption to mortality differentials in India.

Methods and Findings

Cross-sectional data on 217 363 individuals from 41 554 households from the 2004–2005 India Human Development Survey was analyzed using multiple logistic regressions. Mortality differentials across social castes were attenuated after adjusting for household economic factors such as income and assets. Individuals living in the lowest income and assets quintiles had an increased risk of mortality with odds ratio (OR) of 1.66 (95% CI  = 1.23–2.24) in the bottom income quintile and OR of 2.94 (95% CI  = 1.66–5.22) in the bottom asset quintile. Counter-intuitively, individuals living in households with lowest monthly consumption per capita had significantly lower probability of death (OR  = 0.27, 95% CI  = 0.20–0.38).

Conclusions

Mortality burden in India is largely patterned on economic dimensions as opposed to caste dimensions, though caste may play an important role in predicting economic opportunities.     

Incidence and Predictors of End Stage Renal Disease among Low-Income Blacks and Whites

We evaluated whether black race is associated with higher incidence of End Stage Renal Disease (ESRD) among a cohort of blacks and whites of similar, generally low socioeconomic status, and whether risk factor patterns differ among blacks and whites and explain the poorly understood racial disparity in ESRD. Incident diagnoses of ESRD among 79,943 black and white participants in the Southern Community Cohort Study (SCCS) were ascertained by linkage with the United States Renal Data System (USRDS) from 2002 through 2009. Person-years of follow up were calculated from date of entry into the SCCS until date of ESRD diagnosis, date of death, or September 1, 2009, whichever occurred first. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for incident ESRD among black and white participants in relation to baseline characteristics. After 329,003 person-years of follow-up, 687 incident cases of ESRD were identified in the cohort. The age-adjusted ESRD incidence rate was 273 (per 100,000) among blacks, 3.5-fold higher than the rate of 78 among whites. Risk factors for ESRD included male sex (HR = 1.6; 95% CI 1.4–1.9), low income (HR = 1.5; 95% CI 1.2–1.8 for income below vs. above $15,000), smoking (HR = 1.2; 95% CI 1.02–1.4) and histories of diabetes (HRs increasing to 9.4 (95% CI 7.4–11.9) among those with ≥20 years diabetes duration) and hypertension (HR = 2.9; 95% CI 2.3–3.7). Patterns and magnitudes of association were virtually identical among blacks and whites. After adjustment for these risk factors, blacks continued to have a higher risk for ESRD (HR = 2.4; 95% CI = 1.9–3.0) relative to whites. The black-white disparity in risk of ESRD was attenuated but not eliminated after control for known risk factors in a closely socioeconomically matched cohort. Further research characterizing biomedical factors, including CKD progression, in ESRD occurrence in these two racial groups is needed.     

Incidence of and Risk Factors Associated with Pulmonary and Extra-Pulmonary Tuberculosis in Saudi Arabia (2010–2011)

Setting

National Tuberculosis Program, Department of Public Health, Ministry of Health, Kingdom of Saudi Arabia (KSA).

Objective

To summarize data on the incidence of tuberculosis and associated risk factors for cases reported during 2010–2011.

Design

Retrospective analysis of routinely collected data through an established national disease notification system of the Ministry of Health in KSA.

Results

The estimated incidence of all forms of tuberculosis fell from 15.8/100000 (95% CI: 15.3/100,000–16.3/100,000) in 2010 to 13.8/100,000 (95% CI: 13.4/100,000–14.2/100,000) in 2011. Saudis experienced a decrease from 11.8/100,000 (95% CI: 11.3/100,000 to 12.3/100,000) in 2010 to 9.9/100,000 (95% CI: 9.5/100,000–10.4/100,000) in 2011 while the incidence in non-Saudis declined from 24.7/100,000 (95% CI: 23.6/100,000 to 25.7/100,000) in 2010 to 22.5/100,000 (95% CI: 21.5/100,000 to 23.4/100,000) in 2011. The proportion of Extra Pulmonary TB (EPTB) which increased minimally from 30% in 2010 to 32% in 2011 was higher than global figures and strongly associated with age, sex, nationality and occupation.

Conclusion

The current estimated incidence of about 14/100,000 in 2011 is less than half its estimated value of 44/100000 in 1990. Without prejudice to any under-reporting, the KSA appeared to be on the course for TB elimination by 2050 having reached the first milestone set by WHO. The proportion of EPTB remains higher than global figure and age, sex, nationality and occupation were significant independent predictors of EPTB.     

The Incidence and Survival Rate of Population-Based Pancreatic Cancer Patients: Shanghai Cancer Registry 2004–2009

Background

Pancreatic cancer is a devastating disease with dismal prognosis. Large population-based evidence on its survival rate and influence factors is lacking in China.

Objective

This study aimed to depict the demographic factors, tumor characteristics, incidence rate and survival rate of pancreatic cancer cases in urban China.

Methods

The demographic factors, tumor characteristics were collected for all the pancreatic cancer cases identified during 2004 to 2009 from the Shanghai Cancer Registry. The survival time was ascertained through linkage of the Shanghai Cancer Registry and the Shanghai Vital Statistics Registry. The deadline of death certificates was the end of December 2012. Kaplan-Meier method and Cox proportional-hazards regression model were used to explore the survival rate and influence factors.

Results

11,672 new pancreatic cancer cases were identified among Shanghai residency during 2004 to 2009. The crude incidence rate of pancreatic cancer was increasing from 12.80/100,000 in 2004 to 15.66/100,000 in 2009, while the standardized incidence rate was about 6.70/100,000 and didn''t change a lot. The overall 5-year survival rate was 4.1% and the median survival time was 3.9 (95% Confidence Interval (CI) 3.8–4.0) months. Subjects had received surgical resection had improved survival (HR  = 0.742, 95% CI: 0.634–0.868) than its counterparts. In adjusted multivariable Cox proportional-hazard models, factors associated with poor survival included older age at diagnosis (age > = 70 years: hazard ratio (HR)  = 1.827, 95% CI: 1.614–2.067), male sex (HR  = 1.155, 95% CI: 1.041–1.281), distant disease at diagnosis (HR =  1.257, 95% CI: 1.061–1.488), positive lymph node (HR  = 1.236, 95% CI: 1.085–1.408), tumor stage (Stage IV HR  = 2.817, 95% CI: 2.029–3.909).

Conclusion

The age-adjusted incidence rate was stable and overall survival rate was low among pancreatic cancer patients of Shanghai residency. Early detection and improved treatment strategies are needed to improve prognosis for this deadly disease.     

Impact of Income Inequality and Other Social Determinants on Suicide Rate in Brazil

Studies about suicide worldwide have mainly focused on individual-level psychiatric risk factors. In Brazil, suicide is an important public health problem. Brazil has evidenced important socioeconomic changes over the last decades, leading to decreasing income inequality. However, the impact of income inequality on suicide rate has never been studied in the country.

Purpose

To analyze whether income inequality and other social determinants are associated with suicide rate in Brazil.

Method

This study used panel data from all 5,507 Brazilian municipalities from 2000 to 2011. Suicide rates were calculated by sex and standardized by age for each municipality and year. The independent variables of the regression model included the Gini Index, per capita income, percentage of individuals with up to eight years of education, urbanization, average number of residents per household, percentage of divorced people, of Catholics, Pentecostals, and Evangelicals. A multivariable negative binomial regression for panel data with fixed-effects specification was performed.

Results

The Gini index was positively associated with suicide rates; the rate ratio (RR) was 1.055 (95% CI: 1.011–1.101). Of the other social determinants, income had a significant negative association with suicide rates (RR: 0.968, 95% CI: 0.948–0.988), whereas a low-level education had a positive association (RR: 1.015, 95% CI: 1.010–1.021).

Conclusions

Income inequality represents a community-level risk factor for suicide rates in Brazil. The decrease in income inequality, increase in income per capita, and decrease in the percentage of individuals who did not complete basic studies may have counteracted the increase in suicides in the last decade. Other changes, such as the decrease in the mean residents per household, may have contributed to their increase. Therefore, the implementation of social policies that may improve the population’s socioeconomic conditions and reduce income inequality in Brazil, and in other low and middle-income countries, can help to reduce suicide rates.     

Incidence and Risk of Proteinuria with Aflibercept in Cancer Patients: A Meta-Analysis

Background

Aflibercept is a human recombinant fusion protein with antiangiogenic effects that functions as a decoy receptor to bind vascular endothelial growth factor A. Proteinuria is one of its major adverse effects with a substantial variation in the incidence rate, and the overall risk of proteinuria has not been systematically studied. We performed a meta-analysis of published clinical trials to quantify the incidence and relative risk of proteinuria in cancer patients treated with aflibercept.

Methods

The electronic databases were searched, including PubMed, Embase, Cochrane databases, and ASCO (American Society of Clinical Oncology) abstracts. Eligible studies were phase II and III prospective clinical trials of cancer patients treated with aflibercept with toxicity data on proteinuria. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated using fixed or random effects models depending on the heterogeneity of the included studies.

Results

A total of 4,596 patients with a variety of solid tumors from 16 prospective clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade proteinuria in cancer patients were 33.9% (95% CI: 27.3–42.1%) and 7.9% (95% CI: 6.1–10.2%). The relative risks of proteinuria of aflibercept compared to control were increased for all-grade (RR = 1.41, 95% CI: 1.13–1.77) and high-grade (RR = 6.18, 95% CI: 3.78–10.12) proteinuria. The risk of developing all-grade and high-grade proteinuria with aflibercept was substantially higher than that of bevacizumab (all-grade: RR 1.85, 95% CI: 1.63–2.11; high-grade: RR 2.37, 95% CI: 1.84–3.05).

Conclusions

Aflibercept is associated with an increased risk of developing proteinuria. Appropriate monitoring and treatment is strongly recommended to prevent potential renal damage. Future studies are still needed to investigate the risk reduction and possible use of aflibercept in cancer patients.     

The incidence of optic neuritis in Split-Dalmatia county, Croatia

The aim of the study was to determine the incidence of monosymptomatic optic neuritis (MON) in residents of Split-Dalmatia County, Croatia. The 127 cases (83 female, aged 26.2+/-9.9 and 44 male aged 26.9+/-11.2) with MON presented between January 1985 and December 2001 were analyzed from hospital data. The annual incidence was 1.6 per 100,000 (95% CI, 0-3). The incidence among females was 2.2 (95% CI, 0-4.6) cases / 100,000 per year and 1.1 (95% CI, 0-3) among males. The difference in incidence rates for women vs. men was not significant (chi2=0.41; p=0.52), although it is more likely that a true difference exists. The peak incidence in both sexes observed in the group 20-29 years of age was 4.2 (95% CI, 0-10). The highest incidence of MON was found in spring (46 cases). In summary, the incidence of MON in Split-Dalmatia County during the 17 years period is relatively low.     

Incidence and Geographical Variation of Amyotrophic Lateral Sclerosis (ALS) in Southern Germany – Completeness of the ALS Registry Swabia

Objective of this paper was to investigate the incidence, potential geographical clusters and the completeness of the amyotrophic lateral sclerosis (ALS) registry in Southern Germany (Swabia).Age-standardized incidence rates (ASR) and ratios (SIR) as well as 95% confidence intervals (CI) were estimated at county level. Capture-recapture (CARE) procedures were applied taking data source dependency into account to estimate the quality of case ascertainment in the ALS registry Swabia. We identified 438 ALS cases (53% men, 47% women) in the target population of about 8.4 Mio inhabitants. The gender ratio (men∶women) was 1.1∶1. The mean age at onset of ALS was 63.8 (SD = 11.9) years for men and 66.0 (12.2) for women. The age distribution peaked in the age group 70–74 years. The ASR of ALS was 2.5 per 100,000 person years (PY; 95% CI: 2.3–2.7). The mean SIR was 1.1 per 100,000 PY (95% CI: 1.0–1.2). High SIR suggesting geographical clusters were observed in two counties (Göppingen and Bodenseekreis), but the variation was not statistically significant (p-values = 0.2 and 0.5). The percentage of CARE estimated missing cases was 18.9% in the registry yielding an ASR of 3.1 per 100,000 PY. The high coverage of the CARE estimated completeness of the ALS registry Swabia indicates excellent quality for future projects. Regional variations have to be investigated further.     

Insight to the Epidemiology and Risk Factors of Extrapulmonary Tuberculosis in Tianjin,China during 2006-2011

Background

The proportion of extrapulmonary tuberculosis (EPTB) among all the reported tuberculosis (TB) cases has increased in different populations. Despite the large burden of TB in China, the epidemiology of EPTB in China remains largely understudied and the risk factors for having EPTB diagnosis in China have not been identified.

Methods

To gain insight to EPTB epidemiology in China, we analyzed TB surveillance data collected in Tianjin, China, during 2006 to 2011. The frequency of EPTB among all TB cases and within different socio-demographic groups of the study patients aged 15 years and older was determined for EPTB in general and by specific types. The distribution of socio-demographic characteristics was compared between pulmonary TB (PTB) group and EPTB group by chi-square test. Crude and multiple logistic regression-derived adjusted odds ratios (aOR) and 95% confidence intervals (CI) were determined to assess the associations between having EPTB diagnosis and each individual explanatory variable in question.

Results

About one-tenth (1,512/14,561) of the patients investigated in this study had EPTB. Of these 1,512 EPTB cases, about two thirds were pleural TB. Significant difference in age, occupation, and urbanity of residence were found between PTB and EPTB groups (p<0.05). Patients with EPTB diagnosis were more likely to be 65 years or older (aOR = 1.22, 95% CI: 1.02, 1.46), to be retired (aOR = 1.37, 95% CI: 1.08, 1.75), and to live in urban areas (aOR = 1 38, 95% CI: 1.22, 1.55).

Conclusions

The findings of this study extends the knowledgebase of EPTB epidemiology in developing countries and highlight the need for improved EPTB detection in China, especially in subpopulations with high risk for EPTB or having limited access to medical facilities with adequate capacity for EPTB diagnosis.     

Risk of developing active tuberculosis following tuberculosis screening and preventive therapy for Tibetan refugee children and adolescents in India: An impact assessment

BackgroundTuberculosis (TB) rates among Tibetan refugee children and adolescents attending boarding schools in India are extremely high. We undertook a comprehensive case finding and TB preventive treatment (TPT) program in 7 schools in the Zero TB Kids project. We aimed to measure the TB infection and disease burden and investigate the risk of TB disease in children and adults who did and did not receive TPT in the schools.Methods and findingsA mobile team annually screened children and staff for TB at the 7 boarding schools in Himachal Pradesh, India, using symptom criteria, radiography, molecular diagnostics, and tuberculin skin tests. TB infection (TBI) was treated with short-course regimens of isoniazid and rifampin or rifampin. TB disease was treated according to Tibetan and Indian guidelines. Between April 2017 and December 2019, 6,582 schoolchildren (median age 14 [IQR 11–16] years) and 807 staff (median age 40 [IQR 33–48] years) were enrolled. Fifty-one percent of the students and 58% of the staff were females. Over 13,161 person-years of follow-up in schoolchildren (median follow-up 2.3 years) and 1,800 person-years of follow-up in staff (median follow-up 2.5 years), 69 TB episodes occurred in schoolchildren and 4 TB episodes occurred in staff, yielding annual incidence rates of 524/100,000 (95% CI 414–663/100,000) person-years and 256/100,000 (95% CI 96–683/100,000) person-years, respectively. Of 1,412 schoolchildren diagnosed with TBI, 1,192 received TPT. Schoolchildren who received TPT had 79% lower risk of TB disease (adjusted hazard ratio [aHR] 0.21; 95% CI 0.07–0.69; p = 0.010) compared to non-recipients, the primary study outcome. Protection was greater in recent contacts (aHR 0.07; 95% CI 0.01–0.42; p = 0.004), the secondary study outcome. The prevalence of recent contacts was 28% (1,843/6,582). Two different TPT regimens were used (3HR and 4R), and both were apparently effective. No staff receiving TPT developed TB. Overall, between 2017 and 2019, TB disease incidence decreased by 87%, from 837/100,000 (95% CI 604–1,129/100,000) person-years to 110/100,000 (95% CI 36–255/100,000) person-years (p < 0.001), and TBI prevalence decreased by 42% from 19% (95% CI 18%–20%) to 11% (95% CI 10%–12%) (p < 0.001). A limitation of our study is that TB incidence could be influenced by secular trends during the study period.ConclusionsIn this study, following implementation of a school-wide TB screening and preventive treatment program, we observed a significant reduction in the burden of TB disease and TBI in children and adolescents. The benefit of TPT was particularly marked for recent TB contacts. This initiative may serve as a model for TB detection and prevention in children and adolescents in other communities affected by TB.

Kunchok Dorjee and colleagues investigate infection and disease burden following mass tuberculosis preventive treatment for Tibetan refugee children at schools in India.     

Esophageal cancer in relation to alcohol drinking and tobacco use among men in Kerala,India – Karunagappally cohort

BackgroundIn the Karunagappally cohort, esophageal cancer is the third most common cancer with an age-adjusted incidence rate of 6.2 per 100,000 person-years among men. The present study analyzed the risk of esophageal cancer in relation to alcohol drinking and tobacco use.MethodsThe study included 65,528 men aged 30–84 years in the Karunagappally cohort, India.ResultsPoisson regression analysis showed that alcohol drinking significantly increased (P = 0.027) the risk of esophageal cancer and the relative risk (RR) for current drinkers was 1.6, (95 % confidence interval (CI) = 1.1–2.3). The risk increased significantly in heavy alcohol drinkers (250 g of ethanol or above per day) (RR = 2.1, 95 % CI = 1.2–3.5) (P for trend = 0.014) and among current arrack consumers (RR = 1.8, 95 % CI = 0.99–3.29) (P for trend = 0.025). Current bidi and cigarette smokers showed an increase in the trend of cancer risk. A significantly higher risk was seen in those who had started smoking bidi before the age of 18 years, RR = 1.9 (95 % CI = 1.1–3.3) (P for trend = 0.044). Furthermore, increased RR for heavy bidi and cigarette smokers were 1.6 (95 % CI = 1.1–2.5) and 2.4 (95 % CI = 1.3–4.5), respectively.ConclusionTo the best of our knowledge, this is the first cohort study in India to report an increased esophageal cancer risk with respect to alcohol drinking.     

Incidence of multiple myeloma in Kailuan cohort: A prospective community-based study in China

BackgroundPrevious retrospective studies showed that the incidence and mortality rates for MM in China were lower than those in western countries. A large-scale prospective study on incidence and mortality rates of MM is still lacking.MethodsBased on the prospective Kailuan Cohort study in China, we included all patients with MM in Kailuan Cohort from June 1, 2008 to December 31, 2016. Using the numbers of diagnosed cases and deaths during the study period as the numerators and the corresponding observed person-years as the denominators respectively, we calculated crude incidence and mortality rates. The 95% confidence intervals for crude incidence rate and mortality rate were estimated base on Poisson distribution. Rates were standardized by direct standardization according to the China population in 2000 and Segi’ world standard population.ResultsA total of 22 members from Kailuan Cohort were first diagnosed with MM between 2008 and 2016. The calculated crude incidence rates were 2.8 (95% CI, 1.7–4.2) per 100,000 person-years for all participants. The standardized incidence rate was 0.9 per 100,000 person-years (95% CI, 0.5–2.1) when standardized by 2000 China population census data, and 1.0 per 100,000 person-years (95% CI, 0.6–1.8) when standardized by Segi’s world standard population (WSP). The calculated crude mortality rates were 2.3 (95% CI, 1.4–3.6) per 100,000 person-years. The mortality standardized by 2000 China population census data was 0.7 per 100,000 person-years (95% CI, 0.3–1.9), and 0.9 per 100,000 population (95% CI, 0.5–1.7) when standardized by Segi’s WSP. Both incidence and mortality for males were higher than that for females almost in all age groups. Both rates increased steadily with age.ConclusionIn this community-based prospective cohort study, we found that the incidence of MM in China was far lower than that in American and Europe.     

Association between B Vitamins Supplementation and Risk of Cardiovascular Outcomes: A Cumulative Meta-Analysis of Randomized Controlled Trials

Background

Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs) investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base.

Methodology and Principal Findings

In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR) was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE) occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI) occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93–1.03; P = 0.37), total mortality (RR, 1.01; 95% CI: 0.97–1.05; P = 0.77), cardiac death (RR, 0.96; 95% CI: 0.90–1.02; P = 0.21), MI (RR, 0.99; 95% CI: 0.93–1.06; P = 0.82), or stroke (RR, 0.94; 95% CI: 0.85–1.03; P = 0.18).

Conclusion/Significance

B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.     

Excess Mortality Associated with Influenza among Tuberculosis Deaths in South Africa, 1999–2009

Background

Published data on the interaction between influenza and pulmonary tuberculosis (PTB) are limited. We aimed to estimate the influenza-associated mortality among individuals with PTB in South Africa from 1999–2009.

Methods

We modelled the excess influenza-associated mortality by applying Poisson regression models to monthly PTB and non-tuberculosis respiratory deaths, using laboratory-confirmed influenza as a covariate.

Results

PTB deaths increased each winter, coinciding with influenza virus circulation. Among individuals of any age, mean annual influenza-associated PTB mortality rate was 164/100,000 person-years (n = 439). The rate of non-tuberculosis respiratory deaths was 27/100,000 (n = 1125) for HIV-infected and 5/100,000 (n = 2367) for HIV-uninfected individuals of all ages. Among individuals aged <65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-infected (relative risk (RR): 5.2; 95% CI: 4.6–5.9) and HIV-uninfected individuals (RR: 61.0; CI: 41.4–91.0). Among individuals aged ≥65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-uninfected individuals (RR: 13.0; 95% CI: 12.0–14.0).

Conclusion

We observed an increased risk of influenza-associated mortality in persons with PTB compared to non-tuberculosis respiratory deaths. If confirmed in other settings, our findings may support recommendations for active inclusion of patients with TB for influenza vaccination and empiric influenza anti-viral treatment of patients with TB during influenza epidemics.     

Public Transportation and Tuberculosis Transmission in a High Incidence Setting

BackgroundTuberculosis (TB) transmission may occur with exposure to an infectious contact often in the setting of household environments, but extra-domiciliary transmission also may happen. We evaluated if using buses and/or minibuses as public transportation was associated with acquiring TB in a high incidence urban district in Lima, Peru.MethodsNewly diagnosed TB cases with no history of previous treatment and community controls were recruited from August to December 2008 for a case-control study. Crude and adjusted odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to study the association between bus/minibus use and TB risk.ResultsOne hundred forty TB cases and 80 controls were included. The overall use of buses/minibuses was 44.9%; 53.3% (72/135) among cases and 30.4% (24/79) among controls [OR: 3.50, (95% CI: 1.60–7.64)]. In the TB group, 25.7% (36/140) of subjects reported having had a recent household TB contact, and 13% (18/139) reported having had a workplace TB contact; corresponding figures for controls were 3.8% (3/80) and 4.1% (3/73), respectively[OR: 8.88 (95% CI: 2.64–29.92), and OR: 3.89 (95% CI: 1.10–13.70)]. In multivariate analyses, age, household income, household contact and using buses/minibuses to commute to work were independently associated with TB [OR for bus/minibus use: 11.8 (95% CI: 1.45–96.07)].ConclusionsBus/minibus use to commute to work is associated with TB risk in this high-incidence, urban population in Lima, Peru. Measures should be implemented to prevent TB transmission through this exposure.     

Diabetes Mellitus and Risk of Bladder Cancer: A Meta-Analysis of Cohort Studies

Background

Increasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. To provide a quantitative assessment of this association, we evaluated the relation between DM and incidence and mortality of bladder cancer in an updated meta-analysis of cohort studies. Methods We identified cohort studies by searching the EMBASE and MEDLINE databases, through 31 March 2012. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random-effects models.

Results

A total of 29 cohort studies (27 articles) were included in this meta-analysis. DM was associated with an increased incidence of bladder cancer (RR 1.29, 95% CI: 1.08–1.54), with significant evidence of heterogeneity among these studies (p<0.001, I² = 94.9%). In stratified analysis, the RRs of bladder cancer were 1.36 (1.05–1.77) for diabetic men and 1.28 (0.75–2.19) for diabetic women, respectively. DM was also positively associated with bladder cancer mortality (RR 1.33, 95% CI: 1.14–1.55), with evident heterogeneity between studies (p = 0.002, I² = 63.3%). The positive association was observed for both men (RR 1.54, 95% CI: 1.30–1.82) and women (RR 1.50, 95% CI: 1.05–2.14).

Conclusion

These findings suggest that compared to non-diabetic individuals, diabetic individuals have an increased incidence and mortality of bladder cancer.     

The association of extreme temperatures and the incidence of tuberculosis in Japan

Seasonal variation in the incidence of tuberculosis (TB) has been widely assumed. However, few studies have investigated the association between extreme temperatures and the incidence of TB. We collected data on cases of TB and mean temperature in Fukuoka, Japan for 2008–2012 and used time-series analyses to assess the possible relationship of extreme temperatures with TB incident cases, adjusting for seasonal and interannual variation. Our analysis revealed that the occurrence of extreme heat temperature events resulted in a significant increase in the number of TB cases (relative risk (RR) 1.20, 95 % confidence interval (CI) 1.01–1.43). We also found that the occurrence of extreme cold temperature events resulted in a significant increase in the number of TB cases (RR 1.23, 95 % CI 1.05–1.45). Sex and age did not modify the effect of either heat or cold extremes. Our study provides quantitative evidence that the number of TB cases increased significantly with extreme heat and cold temperatures. The results may help public health officials predict extreme temperature-related TB incidence and prepare for the implementation of preventive public health interventions.