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.     

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).     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

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 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.     

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

Background

Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.

Methods

552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.

Results

The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.

Conclusion

Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy.