Search

AbstractAimsJapanese cedar pollinosis (JCP) is a form of seasonal allergic rhinitis that affects 38.8% of the Japanese population. Particularly severe and most severe symptoms among JCP patients can lead to impairments of paid work productivity and unpaid work activities. Indeed, the current standard of care (SoC) is not always able to relieve these symptoms. Omalizumab, a novel JCP treatment recently approved in Japan, provides an effective add-on therapy to the SoC. This study estimates the effect of omalizumab on paid and unpaid work activities (i.e. its social impact) in patients with severe and most severe JCP symptoms in Japan.MethodsThe impact of omalizumab was estimated through a one-year static cohort model using the Work Productivity and Activity Impairment Allergy Specific (WPAI-AS) questionnaire derived from a clinical trial on omalizumab enrolling patients with severe and most severe JCP symptoms, which had been conducted in Japan. This effect was quantified using Japanese official statistics on employment and time use. The human capital approach and the proxy good approach were employed to monetize paid and unpaid work activities, respectively. A sensitivity analysis was implemented to account for modeling structural uncertainties.ResultsOur results show that the use of omalizumab might reduce the paid and unpaid work productivity losses due to severe and most severe JCP by nearly one-third. In the severe symptom period of three weeks, 36.6 million hours of lost paid and unpaid work hours could be avoided, which sums up to a monetized productivity loss of 728.3 million USD.ConclusionsOmalizumab could provide substantial benefits in terms of paid and unpaid work activities in patients with severe and most severe JCP. Our results also highlight the importance of considering unpaid work in estimating productivity costs due to poor health.

Coronary fistula is a rare form of congenital heart disease and is defined as an abnormal connection between a coronary branch and a cardiac chamber or a large intrathoracic vessel without the interposition of the capillary circulation. The right coronary artery is the most common site of origin for coronary fistula. Other sites include the left anterior descending artery and left circumflex artery. The clinical presentation and the natural history can be extremely variable depending on the patient‘s age, fistula size, and anatomy. Small to medium–sized coronary fistulas may be asymptomatic. Large fistulas can manifest with angina pectoris due to myocardial ischemia secondary to the coronary steal phenomenon. Shunting through large fistulas can have hemodynamic consequences secondary to volume overload in the pulmonary or systemic circulation, leading to symptoms and signs of heart failure. We describe the case of an 83–year–old woman recently undergoing TAVI and suffering from primary myelofibrosis requiring periodic transfusions. Pre–TAVI coronary angiography showed coronary vessels free from significant hemodynamic lesions and multiple coronary–ventricular fistulas draining into the left ventricle. Total body aortic CT angiography did not reveal other abnormal vascular connections. One month after the aortic valve correction procedure, the patient presented with heart failure (HfpEF). At a recent follow–up visit, diuretic therapy was discontinued due to the successful correction of aortic valve disease and normal ejection fraction. Due to further anemization from the underlying hematologic condition, the patient underwent blood transfusion with worsening of dyspnea despite correction of hemoglobin levels. Discontinuation of diuretic therapy and transfusion of red blood cell units resulted in volume overload with worsening clinical condition. The presence of multiple coronary fistulas precluded an interventional approach, but therapeutic optimization and reintroduction of diuretic therapy restored the patient‘s hemodynamic compensation. Usually fistulas drain into the low–pressure venous circulation like right ventricle and right atrium. This case represents a rare instance of multiple left coronary fistulas draining into the left ventricle (only 3% of cases). Aortic valve correction may have further reduced left ventricular telediastolic pressures, worsening the shunt of coronary fistulas resulting in heart failure due to volume overload.

The aim of the present study is to compare the performance of several commercial human papillomavirus (HPV) tests in a cohort of 281 women. The hybrid capture II, the PreTect-HPV-Proofer, the linear array, and DR.HPV™IVD were utilized to detect and type HPV in parallel with in-house PCR tests followed by direct automated sequencing or by sub-cloning and sequencing. The concordance levels along with other tests were evaluated with a Cohen's K value varying between 0.60 to 0.88, indicating good correlation with nearly perfect agreement between hybrid capture II, (HCII) and the linear array test. High sensitivity was recorded by the linear array and HCII with 100% (95% CI, 0.8021 to 1.0000) detection of cervical intraepithelial neoplasia (CIN) III by both methods. Conversely, the PreTect-HPV-Proofer showed high specificity with 12% (95% CI, 0.7966 to 0.9163) positivity on normal samples. The genotyping analysis showed that agreement among tests was only low to moderate with great differences between different HPV types. Multiple infections were detected with poor concordance and sub-cloning assays revealed the presence of a lower number of HPV in comparison to the other methods. In summary, the use of different HPV tests applied to the same group of cervical smears may possibly lead to incongruent results, suggesting the need to standardize type-specific sensitivity of genotyping methods and the need to evaluate their accuracy in detecting multiple HPV infections. This would be a prerequisite for the use of genotyping assays in cervical cancer screening programs.

RANTES plays a crucial role in cell recruitment in allergic inflammation. We investigated the pharmacological modulation of RANTES release in cultured peripheral blood mononuclear cells obtained from allergic patients with active asthma. Chemokine production was assessed before and after 15 day treatment with histamine-1 receptor antagonists (Loratadine or Cetirizine) and a steroid (Deflazacort), both in unstimulated and PHA-stimulated cell cultures. Results were compared with those obtained from placebo-treated patients. During the treatment period, patients recorded morning and evening peak expiratory flow (PEF) by mini-Wright.PEF absolute values and diurnal variability significantly improved respect to the pre-treatment in steroid-treated patients, in comparison to the placebo and antihistamine-treated groups (p<0.001 and 0.01, respectively). PEF diurnal variability in the antihistamine-treated group were lower than placebo-treated group without statistical significance (p=0.06). No differences could be found in RANTES levels in supernatants of all cultures between the two antihistamines. RANTES release significantly decreased in supernatants of all cell cultures from steroid (p<0.01) and antihistamine (p=0.03 and 0.04) groups after treatments, compared to the basal values; whereas it increased slightly in controls. Co-variance analysis on RANTES levels, adjusting for pre-treatment values, showed a significant reduction of RANTES release by PHA-stimulated PBMCs from steroid (p=0.003) and anti-histamine (p=0.03) groups, with respect to the placebo group. The same statistical tool applied between the steroid and the antihistamine groups showed, after therapy, the lowest levels of RANTES to be associated with steroid treatment (p=0.005). The study shows that steroid is the most effective drug in modulating RANTES release from PBMCs. However, antihistamines, which are able to reduce cell recruitment due to chemokine release, avoiding important side effects, may be useful in long term therapy in controlling and preventing allergic inflammation.

In a previous study, we showed an imbalance in the cytotoxic phenotype of circulating PBMC of IBD patients, possibly related to an alteration in the cytotoxic activity, which might play a role in the immunopathogenesis of IBD. γ/δ T cells, which are increased in the PBMC of IBD patients, represent a minor population of peripheral lymphocytes displaying cytolytic potential and showing both MHC and non-MHC cytotoxicity. This study was performed in order to verify their role in the cytotoxic activity of PBMC from IBD patients and correlate this activity to UC and CD, respectively. We observed a decreased NK cytotoxicity of PBMC in both UC and CD patients and this findings was unrelated to γ/δ T lymphocytes. In fact, both total and γ/δ-depleted PBMC of IBD patients, showed comparable lytic activity. On the contrary, the ADCC lytic activity was within normal range in our patients, ad was not modified by removal of γ/δ cells. The increase of Vδ1+ T cells, previously observed in our patients, seems to be unrelated to this functional impairment, because of a low cytotoxic activity displayed by this subset. Alternatively, the expanded Vδ1+ T cells could be involved in the pathogenesis of the autoimmune phenomena observed in IBD, by a mechanism different from cytotoxicity, such as autoantibodies production and/or loss of tolerance.

A modeling approach for on-line estimation of urea kinetics from continuous measurement of urea concentration in the effluent dialysate stream (DUN) is presented. On-line identification of urea kinetics response parameters is used to predict and update dialysis adequacy during the treatment. Dialysis adequacy can be quantified in several ways, but its strict dependence on final urea concentration is a major fact. For this reason, a good predictive skill on the time course of DUN may enable better performances in the control of dialysis outcome by treatment parameters adjustment. A post-filter enzymatic sensor performs continuous measurement of DUN on patients undergoing standard haemodialysis. To get an early prediction of the end dialysis urea level, the solution of a variable volume double-pool (VVDP) model is used, whose parameters are identified at each time on the basis of the past DUN history. Unlike the variable volume single-pool (VVSP) model, this enables a prompt and accurate estimation of the final DUN. In fact, after 75 min the estimates always differ by less than 10% from the values measured by the sensor at the end of the treatment. Moreover, values predicted by the model in the last hour always lie within 1% of measured final values. Realtime knowledge of an analytic expression for whole DUN time course also enables the accurate prediction of total removed urea, with no need of cumbersome dialysate collection techniques.

We describe an opto-electronic device capable of measuring the hemoglobin concentration (Hgb) non-invasively and continuously, hence the percentage changes in blood volume (BV) during dialysis treatment by means of the optical absorption of monochromatic light by the blood in the arterial line. This method has been validated during several in vitro and in vivo tests, during which the system has shown a low sensitivity to all the common intra-dialytic interference factors, such as oxygen saturation (max. err.=1.6%), blood flow (max. err. =1.8%), osmotic pressure (max. err.=0.7°) and hydraulic pressure (max. err.=0.6°), a high precision (std. err.≤0.1 g/dl) and a good accordance (Hgb mean err.=0.1 g/dl; std. err.=0.38 g/dl; BV mean err.=0.1%; std. err.=1.6%) with the corresponding values derived from standard laboratory tests.

We studied the autonomic reflex response to hypovolemia during HD by means of spectral analysis of heart rate variability (SAHRV) in 10 hypotension prone (group A) and 10 hemodynamically stable patients (group B). UF rate normalized per total body water and blood volume fall were similar in the two groups. The sympatho-vagal balance index, calculated as the ratio between the integrals of the spectrum in the low (0.02-0.15 Hz) and in the high frequency range (0.2-0.35 Hz) rose in group B progressively from the beginning of the treatments, reaching a top at the 90thminute and remained subsequently high until the end. On the contrary this index did not show remarkable increases in group A. The differences between the two groups were statistically significant at 0 (4.6∓2.9 vs 1.5∓1.3), 60th(8.3+7.8 vs 2.2+2.6), 90th(17.9+13.4 vs 3.7+2.8), 150th(8.8+3.7 vs 2.7+2.8) and 210thminute (8.6+5.0 vs 2.9+2.5). In conclusion SAHRV shows an impairment of autonomic reflex response to hypovolemia in hypotension-prone patients.

Due to the crucial role of hypovolemia in the genesis of dialysis-induced hypotension, we have evaluated whether the automatic control of the intradialytic blood volume (BV) decrease along a preset trajectory might be beneficial to the hemodynamic stability during treatment. Five frequently hypotensive HD patients were studied and a 3-period-protocol (A1-B-A2) was adopted, each period lasting 6 sessions per patient. During the B periods the patient BV decrease was kept along a predefined profile, thanks to an automatic system with a retroactive control of both the ultrafiltration rate (UFR) and dialysate conductivity (DC); instead, during the A periods, conventional HD was performed, with linear UFR and constant DC, inducing a spontaneous decrease in BV. The intradialytic BV behaviour was much more stable during the B-periods (-10.2 ∓ 1.4% by the end of the treatment) than during the A1 (-11.2 ∓ 3%) and A2 periods (-11.5 ∓ 2.5%). Only one dialysis-hypotension episode was observed during the B periods, compared to 8 and 5 during the A1 and A2 periods, respectively (p ≤ 0.05). The automatic control of the BV changes during dialysis could improve the intra-treatment cardiovascular stability in critically-ill patients.

This study gives the results in terms of precision and repeatability of a new on-line urea monitoring system (Ureascan P2 Hospal) capable of measuring the urea concentrations in the spent dialysate. The Ureascan P2 Hospal (UP2H), fitted on single-pass dialysis machines (Integra-Hospal), functions by the presence of a disposable mini-reactor containing urease. The passage through the reactor of a minimum quantity of spent dialysate from the filter diluted with a pH 7 buffer solution (1 ml/min) increases its ionic strength, which is detected by a differential measurement of conductivity in proportion to the urea concentration in the dialysis liquid. We studied 13 dialysis sessions, with bicarbonate buffer, in 8 anuric patients. From 4 to 7 dialysate samples were taken during each treatment to determine the urea and 65 samples were analysed overall. Urea values from the UP2H were compared with those measured on the Dimension Du Pont analyser. Simple linear regression analysis showed an excellent correlation between the 2 measuring methods (r=0.987; p<0.001). The Bland-Altman test gave an average difference between the urea values measured with the UP2H and in the laboratory of 1.3±1.2 mg/dl. The agreement limits between 2 SD were - 1.2 mg/dl and +3.8 mg/dl respectively. In conclusion, the UP2H we have developed has proved to be a reliable and very useful instrument for adapting, through the urea kinetic mathematical models, the dialysis dose for individual patients.

A grazing incidence X-ray telescope on board the OSO-IV spacecraft obtained images of the Sun in the 2.5 to 12 Å waveband nearly continuously from 27 October 1967 to 12 May 1968. The instrument had sufficient spatial resolution (one and four arc minutes) and temporal resolution (5 to 20 min) to estimate the spatial characteristics of X-ray emitting regions and to monitor the temporal behavior of individual active regions. Variations in the absence of flares of as much as a factor of 10 in the X-ray output of individual regions were observed, with typical durations ranging from several hours to several days. The X-ray time variations are related to observations at optical and radio wavelengths. The results are interpreted under the assumption that the X-ray time variations are caused by temperature changes in the coronal portions of active regions. The contribution of radiative losses to the energy budget of the coronal active region is estimated.

Continuous recording of beat-to beat changes in haemodynamic parameters such as arterial pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance, was done in 52 uraemic patients. The study was performed during the haemodialysis session, using a system combining a personal computer, an arterial pressure recorder, and an electrical bioimpedance cardiography monitor. Forty-six episodes of dialysis-induced hypotension occurred in 26 patients. Systolic arterial pressure and total peripheral resistance decreased by −39.3±2% and −36.3±4% respectively during acute hypotension; in contrast, there was an increase in cardiac output (+13.9±6.1%), while heart rate and stroke volume did not change significantly. It was possible to distinguish two types of collapse on the basis of heart rate behaviour: the classic ‘tachycardiac’ collapse with heart rate increase and stroke volume decrease, and the so-called ‘bradycardiac’ collapse with a paradoxical reduction in heart rate and an increase in stroke volume. ‘Bradycardiac’ collapses were observed in 54% of the cases. The administration of atropine in one patient resulted in an immediate increase in heart rate. The development of bradycardia and hypotension during haemodialysis seems to be related to a sudden parasympathetic vagal overactivity and could be attributed to the Bezold–Jarish reflex.