House dust mite immunotherapy: A real-world, prescription data-based analysis.

BACKGROUND: House dust mite (HDM) sensitisation can contribute to the development of allergic rhinoconjunctivitis (AR) or allergic asthma (AA). As treatment, allergen immunotherapy (AIT) is a promising approach, since it aims building immunotolerance against allergens, therewith establishing long-term efficacy. The evaluation of AIT has been investigated in many randomised controlled trials, whereas few real-world evidence studies are available. METHODS: We used data from the longitudinal prescription data base IQVIA™ LRx. Data on initial AIT prescriptions against HDM from January 2009 to December 2013 was analysed regarding treatment (subcutaneous AIT with either depigmented polymerised allergen extract [dSCIT] or other allergens [oSCIT], or sublingual immunotherapy [SLIT]) and treatment duration. Treatment groups were compared with a control group of AR patients not receiving AIT. Data on symptomatic medication was collected until February 2017 and progression of AR and AA was compared. RESULTS: Data of 7260 patients with AIT prescriptions and of 21,780 control patients was analysed. AIT was associated with a significant decrease of AR medication intake compared with control (dSCIT: -34.0%, p < 0.0001; oSCIT: -25.7%, p < 0.0001; SLIT: -37.7%, p = 0.0026). In asthmatics, SCIT was associated with a significant decrease of asthma medication compared with control (dSCIT: -45.2%, p < 0.0001; oSCIT: -32.9%, p < 0.0001). Further, a significantly reduced likelihood for onset of asthma medication was demonstrated in patients treated with SCIT compared with controls (dSCIT OR: 0.759, p = 0.0476; oSCIT OR: 0.815, p = 0.0339). CONCLUSION: Real-world data analyses indicate that AIT, particularly given via a subcutaneous route, reduces the need of medication against AR and AA and might delay the onset of asthma medication in patients with AR.

Depigmented-polymerized mixed grass/birch pollen extract immunotherapy is effective in polysensitized patients.

BACKGROUND: Although many patients with allergic rhinoconjunctivitis have symptoms due to sensitization with more than one pollen allergen, and mixed pollen extracts are widely used for allergen immunotherapy in practice, there are few published trials. METHODS: We performed a 2-year multicentre, double-blind, placebo-controlled trial of subcutaneous immunotherapy with mixed depigmented-polymerized birch and grass pollen extract in 285 patients with allergic rhinoconjunctivitis symptomatic during both birch and grass pollen seasons. Primary outcome was combined symptom and medication score (SMS) assessed by daily visual analogue scales (VAS). Analysis included a placebo-based analysis examining the effect of treatment only on days when placebo patients were symptomatic. RESULTS: There was a significant reduction in median SMS for actively treated patients (median 5.70 (interquartile range 2.62-10.02) compared with 7.07 (3.47-10.71) for placebo, P = 0.0385). Rhinitis quality-of-life scores were significantly better for active compared with placebo, and other secondary endpoints were not significantly different. Placebo-based analysis showed a 33.7% reduced SMS at year 2 for active treatment compared with placebo on days when placebo patients were symptomatic. Both birch pollen- and grass pollen-specific IgG4 increased with active treatment. CONCLUSIONS: This study shows efficacy of mixed pollen extracts for immunotherapy for patients symptomatic to both birch and grass pollen allergens. The relatively modest effect may reflect 50% dose reduction for each allergen in the mixture. It supports VAS for symptom assessment and placebo-based analysis as useful for the analysis of immunotherapy trials. The safety of modified extracts may allow study of mixed extracts without dose reduction to improve efficacy.

A randomized placebo-controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy.

BACKGROUND: Specific subcutaneous immunotherapy (SCIT) for seasonal rhinoconjunctivitis with unmodified allergen extracts is effective, but limited by risk of side-effects and involves treatment over 3 years. We examined a depigmented polymerized grass pollen extract for immunogenicity and for clinical efficacy in a rush preseasonal regimen. METHODS: Depigmented polymerized grass pollen extract was tested for proliferation and cytokine production by peripheral blood mononuclear cells. A prospective, double-blind, placebo-controlled trial of 195 grass pollen allergic patients treated with preseasonal rush immunotherapy using depigmented polymerized allergenic extract of mixed grass pollen was performed over 2 years. Primary outcome was combined symptom and medication score (SMS) during the peak of the second grass pollen season. Secondary outcomes included combined score over the whole season, during the first grass pollen season, individual symptom and medication scores, quality of life, well days/hell days and responder analysis. Adverse events were classified using the EAACI scale. Grass pollen-specific IgE and IgG4 were measured before and during treatment. RESULTS: Depigmented polymerized extract stimulated dose-dependent T-cell proliferation and cytokine production. Patients treated with preseasonal SCIT showed improved combined scores during peak season at year 2 (median 3.93, interquartile range 0.77-6.27 vs median 5.86 for placebo, 3.11-8.36, P < 0.01). Most secondary outcomes were significantly better for active treatment. Side-effects were minimal, with no grade 3 or 4 reactions. CONCLUSIONS: Depigmented polymerized grass pollen extract is immunogenic and clinically effective in rush preseasonal SCIT. This form of immunotherapy may be an attractive option for some patients.

Efficacy, safety, and immunological effects of a 2-year immunotherapy with Depigoid birch pollen extract: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Rhinoconjunctivitis due to birch pollen sensitization is common in Northern Europe. A depigmented polymerized birch pollen extract - Depigoid has been developed for immunotherapy. OBJECTIVE: To evaluate its clinical efficacy, safety, and effects on immunological parameters. METHODS: Sixty-one patients aged 7-69 years were included in a randomized, double-blind, placebo-controlled trial of subcutaneous immunotherapy (SCIT) using depigmented polymerized birch pollen extract. SCIT consisted of four increasing doses at 7-day intervals, followed by maintenance injections of 500 DPP (corresponding to 30 microg Bet v1 before depigmentation) at 6-week intervals for 18 months. The primary outcome was the combined symptom and medication score during the 2006 birch pollen season. The frequency of peripheral blood mononuclear cells (PBMC)producing IL-4, IL-10, IL-12, and IL-13 was assessed in a subgroup of patients by ELISPOT assay. RESULTS: After 18 months of treatment, the median combined symptom and medication score (upper/lower quartile) of treated patients was significantly lower than those on placebo: 8.0 (5.8-10.3) and 12.6 (8.6-16.2), respectively (P=0.004). Systemic reactions occurred in 29 patients (12 active, 17 placebo), were grades 1 or 2, and none required specific treatment. After 18 months of treatment, mean serum concentrations of specific IgE increased significantly in both groups (P<0.0001) whereas serum concentrations of both specific IgG1 and IgG4 only increased significantly in the SCIT group (P=0.002) and not in the placebo group. The seasonal increase in numbers of IL-4- and IL-13-producing PBMC was blunted by immunotherapy. CONCLUSIONS: SCIT with depigmented polymerized birch pollen extract significantly reduced symptom and medication scores when compared with the placebo, was well tolerated, and resulted in immunological changes comparable with those of native pollen extracts.

Immunotherapy with depigmented-polymerized mixed tree pollen extract: a clinical trial and responder analysis.

BACKGROUND: Rhinoconjunctivitis because of tree pollen sensitization is common in Northern Europe. Specific subcutaneous immunotherapy (SCIT) is the only disease-modifying treatment, but unmodified allergen extracts carry a risk of allergic side-effects. Our objective was to examine efficacy and safety of a depigmented-polymerized mixed tree pollen extract. METHODS: A double-blind, placebo-controlled trial of 184 tree pollen allergic adults was performed. SCIT consisted of four increasing doses at 7-day intervals, then maintenance injections every 6 weeks for 18 months. Primary outcome was combined symptom and medication score during the 2008 season. Secondary outcomes included analysis at different levels of pollen exposure and a responder analysis. Adverse events were classified using the EAACI scale. Birch pollen-specific IgE and IgG(4) were measured before and after treatment. RESULTS: The combined symptom and medication score of actively treated patients was significantly lower than those on placebo (P < 0.04). Increased efficacy was seen at high pollen exposure (median score 2.1 for active [IQR 0.7-3.4] vs 4.2 [IQR 2.4-5.3] for placebo for days with 500 or more pollen grains per m(3) , a 50% reduction, P < 0.01). A modified responder analysis revealed 64% responders in the active and 32% in the placebo group (P < 0.01). There were 17 systemic reactions. All were mild (grade 1 or 2) and required no treatment. Serum birch-specific IgG(4) increased in the SCIT group (P < .01). CONCLUSIONS: SCIT with depigmented- polymerized tree pollen extract was clinically effective and well tolerated. Responder analysis suggested that one-third of patients treated with immunotherapy may not respond.

Prior approval in the pediatric emergency room.

Managed-care plans for low-income Americans are widely promoted to improve the quality and control the cost of medical care by reducing unnecessary specialty and emergency room (ER) care through the use of primary care physicians as case managers/gatekeepers. The purpose of this study was to evaluate one element of managed care, gatekeeping prior approval, for children who use the pediatric ER of one urban public hospital. Over a 6-month period, 518 children and adolescents insured under managed-care plans that required authorization from the primary care physician to receive treatment presented to the ER. Of the 385 records reviewed for this study, the majority (87%) received their primary care at community health centers or the hospital's own outpatient clinics. Most ER visits (72%) were made when primary care sites were closed. According to nursing triage assessment, 57% presented with urgent or emergent conditions, and 26% had a history of chronic illness. Nine percent required hospitalization. Although an elaborate system for gatekeeping was established, only 13 (3%) patients' requests for ER care were denied. Of these, 3 were seen in the ER without authorization, 6 received the recommended follow-up, and 4 were not seen in follow-up. Twenty-nine participating primary care physicians (74%) and 19 ER staff (63%) responded to a survey of their experience with and attitudes toward prior approval. For a variety of reasons, the majority of primary care physicians and ER staff found the gatekeeping policies for after-hours visits burdensome and inappropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethnic differences in forearm vasodilator capacity.

Previous studies have demonstrated significant ethnic differences in left ventricular structure in both normotensive and hypertensive subjects. To determine if these differences in ventricular geometry are associated with differences in vascular structure, we measured the minimum forearm vascular resistance in 30 healthy young African-American adults and in 30 whites matched for age, gender, and blood pressure. Average daytime blood pressure was determined by ambulatory monitoring during a typical work day. Minimum forearm vascular resistance was measured by plethysmography after 10 minutes of forearm ischemia. Indexed left ventricular mass and relative wall thickness were measured by 2-dimensional-directed M-mode echocardiography. The mean (+/-SD) ambulatory pressure was 126 +/- 11/79 +/- 8 mm Hg in African-Americans and 126 +/- 11/79 +/- 7 mm Hg in whites. The 2 groups were similar in body mass index and in family history of hypertension. African-Americans had a higher minimum forearm vascular resistance than did whites (2.39 +/- 0.75 vs 2.03 +/- 0.55 mm Hg, p <0.05). There was a trend toward a greater left ventricular relative wall thickness in African-Americans (0.38 +/- 0.07 vs 0.35 +/- 0.06, p=0.09). These results suggest that early vascular remodeling is present in African-Americans who do not have established hypertension, and that this ethnic difference in vascular structure is associated with a difference in ventricular geometry.

Why urban voluntary hospitals close.

In this paper, we argue for the importance of understanding hospital closings and relocations. Broad descriptive data on closings, relocations, and other reconfigurations of beds in 52 large and mid-size U.S. cities are presented. The period covered is 1937 to 1980. Two contrasting outlooks on hospital closings and relocations are offered. As hypothesized, smaller and less specialized nonteaching hospitals and those located in minority neighborhoods or serving above-average proportions of minority or Medicaid-funded patients were more likely to close. A potentially more effective but more costly and less accessible system of urban health care appears to result.

Excretion and tissue distribution of 14C-labelled 8-methoxypsoralen in beagle dogs and miniature pigs.

Male beagle dogs and miniature swine were given 14C-labelled 8-methoxypsoralen (8-MOP) as a single oral dose (10 mg/kg body weight). In dogs, there appeared to be wide variability in 8-MOP absorption as indicated by the broad range of percentages of radioactivity recovered from urine and faeces over a 4-day period (3.6-24.7% in urine; 47.3-94.9% in faeces); mean recovery values were 13.6% in the urine and 68.6% in the faeces. In pigs, considerable variability in absorption was also evident, but not to the extent of that seen in dogs. Based on the fraction of the dose recovered in the urine, the absorption of 8-MOP was greater in pigs; the proportion of the dose recovered in urine over a 7-day period ranged from 25.8 to 57.8%. Faecal recovery ranged from 15.4 to 49.0% of the dose. Mean recovery values in pigs were 45.4% in urine and 35.6% in faeces. Most of the 8-MOP was cleared from the bodies of dogs and pigs in a few days, and little 8-MOP residue was sequestered in any of the tissues examined in either species. Small amounts of an 8-MOP-related substance remained in the liver and blood for as long as 4 days in dogs and 7 days in pigs.

Maternal-foetal distribution studies in late pregnancy. I. Distribution of [N-methyl-14C]betaine in tissues of beagle dogs and miniature pigs.

[N-Me-14C]Betaine was administered iv as a single dose (5 mg/kg) to pregnant beagle dogs and miniature pigs late in gestation. Two hr after administration of the radiolabel, when the compound was in equilibrium, the dams were killed and the foetuses were removed for determination of the radioactivity in maternal and foetal tissues. Eight litters of dogs (56 foetuses) and four litters of pigs (30 foetuses) were examined. The distribution of betaine in both species showed distinct differences between maternal and foetal tissues, indicating definite placental barriers; the placental distribution factor was estimated to be 52.3% in dogs and 97.8% in pigs. The blood/brain distribution factor was 84.6% in maternal dogs, 89% in maternal pigs, 65.7% in foetal dogs and 0% in foetal pigs. In the dog, maternal liver was the largest depot of the administered betaine, followed by foetal liver. Foetal heart, lung and kidney tissues also incorporated radiolabelled betaine. The highest concentrations of betaine in the pig were found in maternal kidney and liver.

Maternal-foetal distribution studies in late pregnancy. II. Distribution of [1-14C]acrylamide in tissues of beagle dogs and miniature pigs.

[carbonyl-14C]Acrylamide was administered iv as a single dose (5 mg/kg) to pregnant beagle dogs and miniature pigs late in gestation. After a 2-hr equilibration period, the animals were killed and foetuses were removed for determination of the amount of radioactivity in maternal and foetal tissues. In total, six dog litters (33 foetuses) and seven pig litters (45 foetuses) were examined. In dogs, acrylamide was distributed readily to both maternal and foetal tissues with a placental distribution factor of 17.7%. The blood/brain distribution factor was insignificant (5.9%) in maternal dogs and 0% in the foetuses. Maternal liver was the largest depot of the administered acrylamide in the dog, followed by the maternal kidney. In pigs, the placental distribution factor was 31%, and the blood/brain distribution factor was insignificant in both maternal and foetal pigs. Liver and kidney of maternal pigs also contained the greatest amount of radioactivity. Although there appears to be some placental protection of the foetuses from the xenobiotic in the maternal circulation, foetal brain would be exposed to the effect of any acrylamide present in the foetal circulation, since the foetuses of both species had blood/brain distribution factors that were either small or zero, reflecting the absence of a blood-brain barrier.

The Autosow raised miniature swine as a model for assessing the effects of dietary soy trypsin inhibitor.

Toxicological effects of dietary soy trypsin inhibitor (TI) were assessed in male miniature swine, a model chosen for its similarities to human digestive physiology and anatomy. The TI preparation was extracted from defatted raw soy flour. From 1 through 5 weeks of age, piglets were automatically fed either a TI liquid diet [Autosow TI group (ASTI)] or a control liquid diet [Autosow control group (ASC)]. From 6 to 39 weeks of age, these animals received either swine chow and TI or swine chow and control article. The TI diets were formulated to contain a TI activity of approximately 500 mg TI/100 g dry matter. A sow control (SC) group suckled from birth to 6 weeks of age and then fed as the ASC group with swine chow plus control article from 6 to 39 weeks of age. The SC piglets grew faster than ASC piglets during postnatal weeks 1 and 2; however, the ASC piglets were significantly heavier than the SC piglets (P=0.001) at 6 weeks of age. Compared with the ASC group, TI caused a moderate decrease in feed consumption and a moderate but reversible decrease in growth from 2 to 5 weeks of age, but not thereafter. Some control and TI-fed Autosow-reared piglets had loose stools until 6 weeks of age; the effect was significantly greater in the TI-fed group. Otherwise, all swine were active and had normal appearance and behavior.

Pathological evaluation, clinical chemistry and plasma cholecystokinin in neonatal and young miniature swine fed soy trypsin inhibitor from 1 to 39 weeks of age.

The potential toxicity of dietary soy trypsin inhibitor (TI) was evaluated in neonatal miniature swine. From 1 to 6 weeks of age, two groups of male piglets were artificially reared in an Autosow and automatically fed either TI or control liquid diet. From 6 to 39 weeks of age, these two groups were fed either TI or control chow diet. A third group, sow control (SC), suckled from birth to 6 weeks of age, were also weaned to control chow from 6 to 39 weeks of age. Clinical chemistry and plasma cholecystokinin (CCK) determined at 6, 18, 30 and 39 weeks of age, and serum amylase activity with gross and histopathological analyses of major organs at 6 and 39 weeks of age are reported. TI had no effect on plasma CCK, serum amylase activity, or numerous clinical chemistry values. TI-fed piglets had a larger relative liver weight at 6 weeks of age. Relative pancreas weight decreased with age but was not affected by TI. Gross and histopathological analyses of major organs, except the spleen, were within normal limits. Increased incidence of extramedullary hematopoiesis was noted in the spleen of the TI group at 6 but not at 39 weeks of age. There was no consistent pattern in immunohistochemical foci for secretin, gastrin releasing polypeptide or CCK, and no change in DNA, RNA, mitotic index or nuclear density of pancreatic cells. At 6 weeks of age, TI increased pancreatic protein and amylase activity but not trypsin or chymotrypsin activity. None of the effects suggested that this dose of TI was toxic to either the neonatal or sexually mature miniature male swine.

Body and organ growth of the developing Hormel-Hanford strain of male miniature swine.

As part of a larger study designed to characterize the early developmental stages of the Hormel-Hanford strain miniature pig, whole body, brain, kidney, liver, pancreas and spleen from male animals were examined for weight increases from one to 196 days, the approximate age of maturity. At 196 days, body weights had increased to 82.5 times the weight at day 1; increases in organ weights were greatest for spleen, less and similar for kidney, liver and pancreas, and the least for brain. Little change in relative organ weights was noted, except for the brain where an almost steady decrease occurred starting from 7 days after birth.

Ornithine decarboxylase, fatty acid synthetase, and lipid levels in selected organs of the postnatal developing male miniature pig.

Ornithine decarboxylase (ODC) and fatty acid synthetase (FAS) activities were determined in tissues from male neonate and juvenile miniature swine (Hormel-Hanford strain) at various ages. ODC activity was measured in liver, brain, kidney, pancreas, and spleen at one day and at 1, 4, 8, 12 and between 24 and 32 weeks. Hepatic FAS activity, total lipid, triglyceride, and total cholesterol were measured at 2, 8, 16, and 32 weeks. Generally, tissue ODC activity was highest in the spleen at all ages. Three postnatal patterns of ODC activity were observed for the different organs. The mean values of FAS activity, total lipid, and cholesterol were highest at 8 weeks compared to other sampling periods.

Prevalence and pathogenicity of retroviruses in wildcats in France.

Feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) are frequently encountered in domestic cats (Felis catus) and in wild felids, but only FeLV has been previously identified in wildcats (Fellis silvestris). Thirty-eight wildcats, either captured alive or found dead, were sampled in eastern and central France. Nine of them (23.7 per cent) carried the FeLV p27 antigen, and three (7.9 per cent) had antibodies to FIV. There was a significant relationship between two measures of body condition and FeLV status; the FeLV-positive cats being in poorer condition than the FeLV-negative cats. The results suggest that FeLV is common in wildcats and may increase mortality in this species. The FIV-positive results constitute the first indication of a FIV-related virus in wildcats.

An international dermatological image atlas on the WWW: practical use for undergraduate and continuing medical education, patient education and epidemiological research.

We describe the development of an image database DOIA (Dermatological OnlIne Atlas) and present several spin-off projects using images of the atlas, e.g. student education using the atlas including results of an questionnaire evaluating computer-literacy, prerequisites and interests of students for using computers and the World-Wide-Web (WWW), a patient information system and an experiment to collect epidemiological data from patients with dermatological diseases via WWW. The database, available on the WWW at http:@www.derma.med.uni-erlangen.de, contains about 3,000 clinical images covering more than 540 dermatological diagnoses. It is designed for worldwide use; international submissions are encouraged. One aim of the project is to compile an international reference for dermatological images, containing images of high educational quality and also covering conditions on different skin types and rare diagnoses which are not commonly illustrated in ordinary textbooks. All images were originally mapped to the Erlanger Diagnosis Code, which is a proprietary modified ICD-9 key, later also to the UMLS (Unified Medical Language System). In addition, images are described with keys for the location, physical attributes of the location and clinical and histopathological features of the lesion. In order to facilitate the integration of the atlas into other web-based medical resources and to allow easy access to additional information, the Erlanger Diagnosis Code was mapped to the CUIs (unique concept identifiers) of the UMLS Metathesaurus. One purpose of the UMLS is to allow conversion of terms from one controlled medical vocabulary to another, thus, mapping of our diagnosis code to the UMLS CUIs allows simultaneous search for a given diagnosis in a number of other databases and also access to our image database from other databases. Mapping was successful for 619 out of 1383 dermatological diagnosis terms. For images with these diagnoses we are able to provide a hyperlink to other databases available on the Internet, such as MEDLINE, PDQ and OMIM, with automatic retrieval using the preferred vocabulary of the respective database. By grouping all diagnoses into sets with similar morphologies we further integrated a differential diagnosis mode. In order to educate patients via the Internet, a separate patient information system has been developed, using images of the electronic atlas. As an experiment to explore the feasibility of the Internet to gather epidemiological data from patients, users are asked to complete an electronic questionnaire covering signs for atopy. We conclude that an online image atlas has multiple educational, clinical and research applications.