To minimize potential risk of intussusception, the World Health Organization (WHO) recommended in 2009 that rotavirus immunization should be initiated by age 15 weeks and completed before 32 weeks. These restrictions could adversely impact vaccination coverage and thereby its health impact, particularly in developing countries where delays in vaccination often occur.
Methods and Findings
We conducted a modeling study to estimate the number of rotavirus deaths prevented and the number of intussusception deaths caused by vaccination when administered on the restricted schedule versus an unrestricted schedule whereby rotavirus vaccine would be administered with DTP vaccine up to age 3 years. Countries were grouped on the basis of child mortality rates, using WHO data. Inputs were estimates of WHO rotavirus mortality by week of age from a recent study, intussusception mortality based on a literature review, predicted vaccination rates by week of age from USAID Demographic and Health Surveys, the United Nations Children’s Fund (UNICEF) Multiple Indicator Cluster Surveys (MICS), and WHO-UNICEF 2010 country-specific coverage estimates, and published estimates of vaccine efficacy and vaccine-associated intussusception risk. On the basis of the error estimates and distributions for model inputs, we conducted 2,000 simulations to obtain median estimates of deaths averted and caused as well as the uncertainty ranges, defined as the 5th–95th percentile, to provide an indication of the uncertainty in the estimates.
We estimated that in low and low-middle income countries a restricted schedule would prevent 155,800 rotavirus deaths (5th–95th centiles, 83,300–217,700) while causing potentially 253 intussusception deaths (76–689). In contrast, vaccination without age restrictions would prevent 203,000 rotavirus deaths (102,000–281,500) while potentially causing 547 intussusception deaths (237–1,160). Thus, removing the age restrictions would avert an additional 47,200 rotavirus deaths (18,700–63,700) and cause an additional 294 (161–471) intussusception deaths, for an incremental benefit-risk ratio of 154 deaths averted for every death caused by vaccine. These extra deaths prevented under an unrestricted schedule reflect vaccination of an additional 21%–25% children, beyond the 63%–73% of the children who would be vaccinated under the restricted schedule. Importantly, these estimates err on the side of safety in that they assume high vaccine-associated risk of intussusception and do not account for potential herd immunity or non-fatal outcomes.
Our analysis suggests that in low- and middle-income countries the additional lives saved by removing age restrictions for rotavirus vaccination would far outnumber the potential excess vaccine-associated intussusception deaths.
Advances in breast cancer research
To mark Breast Cancer Awareness Month, we review some of the many studies published in recent weeks, including research on the effects of screening and on the contributions of various imaging techniques to management of the disease.
Screening halves breast cancer mortality
Breast cancer screening is associated with an average 49% reduction in the risk of dying from the condition, according to the findings of a case-control study. Researchers in Melbourne, Australia, investigated the effects of taking part in the Western Australian population screening program, comparing 427 cases (women who died from breast cancer) with matched controls (up to 10 for each case).
The odds ratio for taking part in the program, in relation to breast cancer mortality, was 0.48 (95% confidence interval 0.38-0.59; p < 0.001), and the researchers said they were unable to find any biases that affected the significance of this finding. An accompanying meta-analysis of similar published case-control studies produced an odds ratio of 0.51.
Overall, said the researchers, the findings “suggest an average 49% reduction in breast cancer mortality for women who are screened”.1
Detecting lymph node metastases
What is the diagnostic value of FDG PET/CT, compared with the standard method using ultrasound, for investigating axillary lymph nodes in breast cancer patients? To find out, specialists in Dusseldorf, Germany, retrospectively studied the records of 90 patients with primary breast cancer who underwent both a whole-body FDG PET/CT scan and an axillary ultrasound scan. The reference standard for the presence of axillary lymph node metastases was the histopathology report.
The researchers found that FDG PET/CT was significantly more accurate than ultrasound for detecting axillary lymph node metastases (75%, compared with 62% for ultrasound; p = 0.019). There was no significant difference between the two methods in sensitivity (54% for FDG PET/CT, 38% for ultrasound; p = 0.0578). FDG PET/CT allowed the detection of extra-axillary loco-regional lymph node metastases that had not been revealed by other imaging methods, in seven patients (8% of the study population).
Concluding, the researchers noted the potential benefits of FDG PET/CT but pointed out that due to its low sensitivity it should not be used as a substitute for sentinel lymph node biopsy.2
Identifying disease relapse
Meanwhile, specialists in Padua, Italy, reported on their study comparing (18F-FDG) PET/CT with CT in patients with breast cancer who had already undergone surgery or other primary treatment. A total of 190 patients had both a PET/CT scan and a CT scan within 3 months, to evaluate disease status.
Overall, 43% of the patients showed evidence of disease relapse. The negative and positive predictive values for relapse were 90% and 72% respectively for PET/CT, compared with 75% and 55% for CT. Regression analyses (both univariate and multivariate) showed that a positive PET/CT scan was significantly associated with disease recurrence.
The researchers concluded that, in women at high-risk of recurrence, PECT/CT imaging could aid the early detection of breast cancer metastases.3
Cancer subtypes show different sonographic features
The different sonographic features of triple-negative breast cancer (negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [Her2]) and non-triple-negative disease were highlighted in a new study by specialists in Bielefeld, Germany.
They retrospectively analysed the records of 315 consecutive breast cancer patients, and found that triple-negative breast cancer (seen in 33 of the patients) was significantly associated with a younger age, a higher tumor grade, and more lymph node involvement.
In terms of sonographic features, the margin of triple-negative breast cancer was significantly more likely to be described as lobulated or microlobulated (75.8% of cases, compared with 49.5% of non-triple-negative breast cancer cases), and less likely to have an echoic halo (39.4% versus 62.8%, respectively). Cooper ligaments were also displaced, instead of disrupted, in triple-negative breast cancer, the researchers said.
They noted that triple-negative breast cancer shares some sonographic features with benign masses, and said understanding the full distinct features of this cancer subtype could help examiners avoid false-negative classification.4
Overview of disease classification
Finally for this overview of recently published research, the current state of breast cancer classification was summarized in a paper published last month. The author, from Milan, Italy, concluded that the established histopathology-based system of classification is of limited value in terms of prognostic ability and predictive power.
Instead, more recent classification schemes based on the assessment of hormone receptor status, Her2 gene over-expression or amplification, and the proliferative fraction, or based on gene expression profiles, “correlate much better with the clinical outcome and may be used to inform the choice of the systemic therapy”.5
- Nickson C, et al. Cancer Epidemiol Biomarkers Prev. 2012;21:1479-88.
- Riegger C, et al. Acta Radiol. 2012 Sep 22 [Epub ahead of print].
- Evangelista L, et al. Q J Nucl Med Mol Imaging. 2012;56:375-84.
- Wojcinski S, et al. J Ultrasound Med. 2012;31:1531-41.
- Viale G. Ann Oncol. 2012;23(suppl 10):x207-10.
Source: Get inside health.