Cost-Effectiveness of Quadrivalent Versus Trivalent Influenza Vaccination in the Dutch National Influenza Prevention Program.

OBJECTIVES: As of 2019, quadrivalent influenza vaccine (QIV) has replaced trivalent influenza vaccine (TIV) in the national immunization program in The Netherlands. Target groups are individuals of 60+ years of age and those with chronic diseases. The objective was to estimate the incremental break-even price of QIV over TIV at a threshold of €20 000 per quality-adjusted life-year (QALY). METHODS: An age-structured compartmental dynamic model was adapted for The Netherlands to assess health outcomes and associated costs of vaccinating all individuals at higher risk for influenza with QIV instead of TIV over the seasons 2010 to 2018. Influenza incidence rates were derived from a global database. Other parameters (probabilities, QALYs and costs) were extracted from the literature and applied according to Dutch guidelines. A threshold of €20 000 per QALY was applied to estimate the incremental break-even prices of QIV versus TIV. Sensitivity analyses were performed to test the robustness of the model outcomes. RESULTS: Retrospectively, vaccination with QIV instead of TIV could have prevented on average 9500 symptomatic influenza cases, 2130 outpatient visits, 84 hospitalizations, and 38 deaths per year over the seasons 2010 to 2018. This translates into 385 QALYs and 398 life-years potentially gained. On average, totals of €431 527 direct and €2 388 810 indirect costs could have been saved each year. CONCLUSION: Using QIV over TIV during the influenza seasons 2010 to 2018 would have been cost-effective at an incremental price of maximally €3.81 (95% confidence interval, €3.26-4.31). Sensitivity analysis showed consistent findings on the incremental break-even price in the same range.

EMG activity of the muscular and stromal layer of the cervix in relation to EMG activity of the myometrium and cervical dilatation in PGF2alpha induced parturition in the cow.

The goal of this study was to quantify and characterize the electromyographic (EMG) activities in the cervical outer muscular layer and in the cervical stromal layer, and to characterize their relationship with myometrial EMG activity and cervical dilatation during PGF2alpha-induced parturition in term pregnant cows. We continuously measured the EMG activity of the uterine myometrium and cervical outer muscular layer as well as the cervical stromal layer in five cows using bipolar electrodes while at the same time measuring changes in the cervical diameter with ultrasound cervimetry. This we did from the moment a prostaglandin analogue was injected until the expulsion of the calf. In contrast to the cervical stromal layer, the cervical outer muscular layer showed distinct EMG activity, which began to increase at about the same time as the EMG activity of the myometrium, i.e. some 12 h before the start of cervical dilatation. However, the rate of this increase was lower than in the myometrium and it was not characterized, like in the myometrium, by an increase in maximum EMG amplitude. Although the cervical outer muscular layer showed contracture and contraction like EMG activity in unison with in the myometrium, it was also characterized by a more irregular EMG activity, which occurred independently from the myometrium. These data suggest that while the outer muscular layer of the cervix may be considered to be a caudal continuation of the myometrium, it also displays activity independently from the myometrium. The physiological relevance of this activity remains to be explored.

High iNOS mRNA and protein levels during early third trimester suggest a role for NO in prelabor cervical ripening in the bovine.

Nitric oxide (NO) plays a key role in the processes leading to cervical softening prior to labor. Inducible nitric oxide synthase (iNOS) contributes most to the increased production of NO during labor, as demonstrated in the rat cervix, or at term pregnancy in women. Changes in expression of iNOS during late gestation have not yet been studied longitudinally in any species, because repeatedly taking biopsies could not be performed. iNOS mRNA (n = 6) and protein expression (n = 3) in serial cervical biopsies of pregnant pluriparous cows taken around days 225, 250, and 275 of pregnancy and within 1.5 hr after calving (d225, d250, d275 and parturition biopsies, respectively) were measured using quantitative RT-PCR and Western blotting. iNOS mRNA expression decreased from the d225 biopsy onwards, differences being significant between the d250 and d275 (P < 0.05) and between the d275 and parturition biopsies (P < 0.05). iNOS protein expression decreased from d225 to d250 onwards. Immunohistochemical analysis of biopsies showed, besides positive staining in endothelium and epithelium, which remained unchanged at different time points, that iNOS expressing cells in the connective tissue cells of early biopsies were predominantly spindle shaped (mostly smooth muscle cells and some fibroblasts). In the parturition biopsies, iNOS reactivity was mainly found in mononuclear leucocytes. These results lead us to suggest that iNOS from spindle shaped cells is involved in prepartum cervical ripening, while iNOS in mononuclear inflammatory cells may be important for local tissue repair mechanisms during postpartum cervical involution.

Validation of pressure measurements and electromyographic results for the uterus of cattle during the early postpartum period.

OBJECTIVE: To evaluate methods for on-farm measurements of uterine contractility in postpartum dairy cows by comparing data simultaneously recorded by use of 2 intrauterine pressure (IUP) devices and quantified electromyographic (EMG) signals. ANIMALS: 5 cows during the first 48 hours after parturition. PROCEDURE: 2 EMG electrodes were implanted on the surface of the gravid uterine horn. Parturition was induced by injection of a prostaglandin F2alpha analogue at day 274 of gestation. An open-tip catheter and pressure microtransducer were transcervically inserted and affixed to a caruncle immediately after calving. Changes in IUP were recorded concurrent with EMG recordings during 2-hour periods at 2, 6, 12, 18, 24, 36, and 48 hours after parturition. Novel acquisition and analysis software programs were used with a digital data-filtering capability for evaluation of IUP and EMG signals. RESULTS: The method for intrauterine fixation of the 2 pressure measurement instruments was effective and allowed easy, externally guided removal of the devices 48 hours after parturition. There was a high correlation between the data obtained by the 2 pressure measuring systems. Good correlation was also found between pressure data obtained by the open-tip catheter system and EMG signals. Although the quantified IUP and EMG signals were highly comparable, synchronization was not always evident during visual inspection of these signals. CONCLUSIONS AND CLINICAL RELEVANCE: The open-tip IUP catheter system with a special fixation method is suitable for use in on-farm studies. It will enable investigators to record natural and pharmacologically influenced uterine contractility in early postpartum dairy cows.