Maximum likelihood estimation of influenza vaccine effectiveness against transmission from the household and from the community

Influenza vaccination is recommended as the best way to protect against influenza infection and illness. Due to seasonal changes in influenza virus types and subtypes, a new vaccine must be produced, and vaccine effectiveness (VE) must be estimated, annually. Since 2010, influenza vaccination has been recommended universally in the United States, making randomized clinical trials unethical. Recent studies have used a monitored household cohort study design to determine separate VE estimates against influenza transmission from the household and community. We developed a probability model and accompanying maximum likelihood procedure to estimate vaccine‐related protection against transmission of influenza from the household and the community. Using agent‐based stochastic simulations, we validated that we can obtain maximum likelihood estimates of transmission parameters and VE close to their true values. Sensitivity analyses to examine the effect of deviations from our assumptions were conducted. We used our method to estimate transmission parameters and VE from data from a monitored household study in Michigan during the 2012‐2013 influenza season and were able to detect a significant protective effect of influenza vaccination against community‐acquired transmission.     

Immediate functional loading of single-tooth TiO2 grit-blasted implant restoration. A controlled prospective study in a porcine model. Part II: Histology and histomorphometry

Background: Evidently, there is a fast‐moving shift from delayed to immediate implant loading. The hypothesis to be tested was that bone reactions adjacent to single TiO₂‐microthreaded implants exposed to immediate masticatory loading for 10 weeks after placement would modulate osseointegration. Materials and Methods: Cylindrical‐ and tapered‐designed implants (Astra Tech AB, Mölndal, Sweden) replaced first and third mandibular premolars respectively in 12 pigs. The animals were allocated into two groups based on soft and hard diet feeding. Each animal received, at random positions, four different masticatory loading conditions: implant with either (1) a cover screw only, (2) a healing abutment, (3) an implant with a crown without occlusal contact, or (4) an implant with a crown in contact with the antagonistic teeth. Results: Histomorphometry showed that there were no statistically significant differences in bone‐implant contact (BIC), bone mass inside/outside of the threads and soft tissue ingrowth ratio for all the implants at 10 weeks after placement irrespective of masticatory loading condition. Bone loss showed a trend of progressive increase for implants with a healing abutment toward implants with occlusal contact. Conclusions: The results of this study rejected the hypothesis and could be explained by the fact that grit‐blasted acid‐etched implants were already placed in dense bone.     

Cytogenetic studies in non-African Burkitt lymphoma

A particular translocation between chromosomes 8 and 14 has been found repeatedly in cytogenetic studies of Burkitt lymphoma, both of African and non-African origin. We report here our findings in cytogenetic studies of direct tumor preparations from 18 non-African Burkitt lymphoma patients, 9 of whom also had cell lines available for study. A t(8;14) was found in direct tumor material in 10 of the 18 patients. Seven of the 9 cell lines had a t(8;14). A total of 15 patients had either a t(8;14) or a 14q+ present in tumor material and/or cell lines. In addition, 8 patients had a peculiar marker chromosome 1. The t(8;14) was not found in every malignant cell and, where present, it was rarely the sole karyotypic abnormality. The relationship of the t(8;14) to the evolution of the tumor is discussed.     

Treated blood pressure, rather than pretreatment, predicts survival in hypertensive patients. A report from the DHSS Hypertension Care Computing Project (DHCCP)

A group of hypertensive patients (n = 2855) with an untreated diastolic blood pressure greater than or equal to 90 mmHg were followed in the Department of Health and Social Security (DHSS) Hypertension Care Computing Project (DHCCP) for periods of up to 10 years. During this period 191 of these patients died. Survival was assessed in relation to pretreatment blood pressure levels and blood pressure achieved during treatment. The blood pressure during treatment was a useful predictor of mortality, but the pretreatment pressure was not. After adjusting for age, mortality was particularly related to the height of the systolic and diastolic blood pressure during the second and third years of treatment. In men, age-standardized 5-year mortality was greater than 10% in those with a first year treated systolic pressure greater than 150 mmHg or a diastolic pressure greater than 95 mmHg. In women, age standardized 5-year mortality was greater than 5% with the same levels of treated blood pressure. The longest survival occurred with the lowest bands of treated pressure, i.e. systolic pressure less than 140 and diastolic pressure less than 90 mmHg; the 5-year mortality being less than 7% in men and less than 3% in women. Treated systolic and diastolic pressures were useful in predicting death from ischaemic heart disease (IHD).     

Factors associated with influenza vaccine receipt in community dwelling adults and their children

Background

Factors associated with influenza vaccine receipt are well studied in healthcare personnel, pregnant women, and the elderly. There has been substantially less research in community dwelling adults and children, and none among entire households. Many studies determine vaccination status by self-report or behavioral intention, outcomes susceptible to misclassification. Given that vaccine is recommended for everyone over six months, re-evaluating these factors is warranted.

Methods

The Household Influenza Vaccine Effectiveness (HIVE) study is a prospective cohort of households with children. In 2010–2011, 549 adults representing 312 households completed surveys evaluating knowledge, attitudes, and practices regarding influenza vaccination for themselves and their children. Using the health belief model (HBM) as a framework, we examined factors associated with documented seasonal influenza vaccine receipt using log-binomial regression models.

Results

In multivariate models, cues to action such as doctor recommendation, (RR 1.62, 95% CI: 1.25–2.10), perceived benefits (RR 1.25, 95% CI: 1.04–1.50), and perceived susceptibility (RR 1.21, 95% CI: 1.03–1.42) were significantly associated with increased likelihood of vaccine receipt among adults while high perceived barriers were associated with decreased likelihood (RR 0.38, 95% CI: 0.25–0.59). Similarly, parents reporting higher barriers were less likely (RR 0.58, 95% CI: 0.42–0.79) and those perceiving greater benefits (RR 4.16, 95% CI: 2.28–7.59) and severity (RR 1.13, 95% CI: 1.00–1.27 were more likely to vaccinate their children. The observed effects of perceptions of susceptibility, severity, and benefits were more pronounced at low cues to action for children, as were the effects of perceptions of barriers and severity among adults.

Conclusion

Perceived benefits and barriers are most strongly associated with vaccine receipt. However, the effects of various factors were most pronounced in the absence of cues to action, which may be an important component of targeted interventions.     

The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques

The detection and quantitation of apoptotic cells is becoming increasingly important in the investigation of the role of apoptosis in cellular proliferation and differentiation. The pathogenesis of hematologic disorders such as aplastic anemia and the development of neoplasia are believed to involve dysregulation of apoptosis. To quantitate accurately the proportion of apoptosis cells within different cell types of a heterogeneous cell population such as blood or bone marrow, a method is required that combines the analysis of large numbers of cells with concurrent immunophenotyping of cell surface antigens. In this study, we have evaluated such a method using the fluorescent DNA binding agent, 7-amino actinomycin D (7AAD), to stain three diverse human cell lines, induced to undergo apoptosis by three different stimuli. Flow cytometric analysis defines three populations on the basis of 7AAD fluorescence and forward light scatter. We have shown by cell sorting and subsequent morphological assessment and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling that the populations defined by 7AAD represent live, apoptotic, and late-apoptotic/dead cells. This method is quick, simple, reproducible, and cheap and will be a valuable tool in the investigation of the role of apoptosis in normal physiology and in disease states.     

The effect of estradiol and a combined estradiol/progestagen preparation on insulin sensitivity in healthy postmenopausal women.

Abnormalities of carbohydrate metabolism and insulin sensitivity have been reported in estrogen deficiency. Estrogen replacement appears to result in an improvement in these parameters, although progestagens may antagonize these effects. We have examined the effects of transdermal estradiol and oral norethisterone on insulin sensitivity using the hyperinsulinemic euglycemic clamp method by performing a randomized, double blind, placebo-controlled study in 22 healthy women after a surgically induced menopause. After baseline measurements, subjects were randomized to receive either transdermal 17beta-estradiol (50 microg) or matching placebo patches for 6 weeks. The subjects were then further randomized to receive either estradiol in combination with oral norethisterone (1 mg) or a matching oral placebo preparation, crossing over after 6 weeks, with assessment of insulin sensitivity at the end of each treatment. No significant increase in insulin sensitivity was observed after 6 weeks of transdermal 17beta-estradiol treatment (95% confidence interval, -0.54, 1.86; P = 0.27). Addition of norethisterone for a further 6 weeks had no detectable effect on insulin sensitivity (95% confidence interval, -1.65, 1.10; P = 0.65). The results of this study using transdermal estradiol do not support previous reports that unopposed estrogens exert potentially beneficial effects on insulin sensitivity and suggest that the addition of an oral progestagen confers no clinically important risk or benefit. It is therefore unlikely that effects on insulin sensitivity contribute appreciably to the cardioprotective benefits attributed to hormone replacement therapy.