Long-term efficacy data for the recombinant zoster vaccine: impact on public health and cost effectiveness in Germany.

The aim of the study was to update previously published public health impact and cost-effectiveness analyses of the recombinant zoster vaccine (RZV), in the German population aged ≥50 years of age (YOA), with the latest vaccine efficacy (VE) estimates against herpes zoster (HZ). The updated estimates are derived from a long-term follow-up study. A previously published multi-cohort Markov model following age cohorts over their lifetime was used. Demographic, epidemiological, cost, and utility data were based on German specific sources. Vaccine coverage was assumed to be 40%, with a second dose compliance of 70%. The estimated VE at time 0 was 98.9% (95% C.I.: 94.0-100%) with an annual waning of 1.5% (95% CI: 0.0-3.4%) for the age group 50-69 YOA. Corresponding values were 95.4% (95% C.I.: 89.7-100%) and 2.3% (95% CI: 0.3-4.4%) for the age group ≥70 YOA. It was estimated that, over the remaining lifetime since vaccination, RZV would prevent approximately 884 thousand (K), 603 K, and 538 K HZ cases in three age cohorts 50-59, 60-69, and ≥70 YOA, respectively. The number needed to vaccinate to prevent one HZ and one postherpetic neuralgia case was 6 and 36 (50-59 YOA cohort), 6 and 34 (60-69 YOA cohort), 10 and 48 (≥70 YOA cohort). The incremental cost-effectiveness ratio of vaccination ranged from €26 K/quality-adjusted life year (QALY) in 60 YOA to €35 K/QALY in 70 YOA. Due to the higher, sustained, RZV VE, improved public health and cost-effectiveness results were observed compared to previous analyses.

PLAIN LANGUAGE SUMMARYWhat is the context?Shingles is a viral infection caused by the reactivation of the chickenpox virus. It causes a painful rash that lasts for several weeks.The incidence and severity of shingles increase with age. In Germany alone there are approximately 400,000 new cases annually.Vaccination can help prevent shingles.Previous studies, based on data collected up to four years post-vaccination, estimated the number of shingles cases prevented. What is new?Here, we use data from the same studies followed over a longer-term to update previous analyses in the German population.We found, based on data up to 8 years following vaccination, that:○ In adults 50-69 years: the vaccine initially prevents 98.9% of cases, with a reduction of 1.5% each year(for example, after one year, it would prevent 97.4% of cases).○ In adults over 70 years of age: the vaccine initially prevents 95.4% of cases, with a reduction of 2.3% each year (for example, after one year, it would prevent 93.1% of cases).○ Vaccination would reduce the number of shingles cases by 0.9 million in a cohort of adults aged 50-59 years, 0.6 million in adults 60-69 years, and 0.5 million in adults older than 70 years, over the remainder of their lifetime.What is the impact?The study provides more certainty regarding results as it is based on the most complete/up to date data. The results showed the potential of Shingrix to prevent shingles while at the same time providing good value for money.

Burden of Herpes Zoster in Adult Patients with Underlying Conditions: Analysis of German Claims Data, 2007-2018.

INTRODUCTION: Several chronic underlying conditions (UCs) are known to be risk factors for developing herpes zoster (HZ) and to increase the severity of HZ and its risk of recurrence. The aim of this study was to investigate the incidence and recurrence of HZ in adult patients with one or multiple UCs. METHODS: A retrospective cohort study based on claims data representing 13% of the statutory health insurance population from 2007 to 2018 in Germany was performed. Patients aged ≥ 18 years were included when at least one of the following UCs was diagnosed: asthma, chronic heart failure, chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), depression, diabetes mellitus type 1 or 2, and rheumatoid arthritis (RA). Exact matching was used to account for differences in the distribution of age and sex between the case and matched control cohorts. Multi-morbidity was considered in sensitivity analyses by analyzing patients with only one UC. RESULTS: Patients with asthma, CHD, COPD, depression, and RA had, on average, a 30% increased risk of developing acute HZ compared to patients without any UC. RA was found to have the highest odds ratio among these conditions, varying from 1.37 to 1.57 for all age groups. Patients with depression also showed a high risk of developing HZ. Analysis of recurrence indicated that patients with at least one UC in the age groups 18-49 years and 50-59 years had the highest risk for a recurrent HZ. After experiencing a first recurrence, patients, regardless of age group, had a two- to threefold higher risk for a second recurrence. CONCLUSION: This study of representative claims data shows a higher HZ incidence and recurrence frequency in patients with UCs. These results provide relevant information for national health care guidelines and disease management programs.

Shingles is caused by the reactivation of the chickenpox virus and is characterized by a painful skin rash with blisters, commonly occurring on the trunk. Underlying conditions (UCs) are conditions that persist for a long time, require ongoing medical attention, and are rarely completely cured (chronic conditions). UCs can increase the severity, the risk, and the frequency of shingles. Here, data from a large German health care insurance provider was used to investigate whether patients with one or more UCs have a higher risk for getting shingles compared to healthy people. In particular, patients with asthma, chronic heart failure, chronic obstructive pulmonary disease, coronary heart disease, depression, diabetes, and rheumatoid arthritis were investigated. The study shows that patients with asthma, coronary heart disease, chronic obstructive pulmonary disease, depression, and rheumatoid arthritis have, on average, a 30% higher risk of developing shingles, regardless of their age. The risk of developing shingles two or more times is also higher for patients with at least one UC, with those aged 18­59 experiencing an even greater risk. It was found that patients with an UC are more exposed to develop shingles and that younger patients have a higher risk of a recurrent episode. The findings provide important information for the development or adaption of national health care guidelines and shingles vaccination recommendations.

Fundamental Frequency of Crying in Two-month-old Boys and Girls: Do Sex Hormones During Mini-puberty Mediate Differences?

OBJECTIVE: To evaluate whether the puberty-like sex hormone surge during the first months of life (mini-puberty) affects fundamental frequency (fo) in infant crying as one would derive from hormone influences on voice in adults. STUDY DESIGN: Populational prospective study. PARTICIPANTS: Twenty healthy normal-hearing infants (nine boys) were recruited for participation. METHODS: Spontaneously uttered cries were collected from each infant at 8 weeks of age. The cries were acoustically analyzed for mean fo and fo range. The fo properties were correlated to the average serum levels of bioavailable estradiol (E2) (mean E2/sex hormone-binding globulin [SHBG]) and testosterone (T) (mean T/SHBG) across the second month of life. RESULTS: Whereas no significant hormone effect was found for mean fo, a significant negative correlation (r = -0.55) was found between fo range and mean E2/SHBG. No indication for a T influence on fo features was found at this age. Although girls showed a slightly higher mean E2 concentration than boys did, the observed differences in cry fo range were judged to be reflective of an infant's serum concentration of E2 rather than a sex-based difference. CONCLUSION: In the absence of laryngeal size differences between female and male infants, the result was interpreted as indicative of an E2 influence on viscoelastic properties of the vocal folds. In our opinion, the investigation of young infants' vocalizations during the early postnatal surge of sex steroids (mini-puberty) may advance our understanding of the mechanisms mediating average sex differences in vocal development and early communication.

Baby babbling at five months linked to sex hormone levels in early infancy.

Gender-dependent differentiation of the brain at morphological, neurochemical and functional levels of organization have been shown to be primarily controlled by sex differences in gonadal hormone concentrations during pre- and early postnatal development. Indeed, previous studies have reported that pre- and perinatal hormonal environments influence brain development and, consequently, affect sex specific long-term language outcomes. Herein, we investigated whether postnatal surges of estrogen (estradiol) and androgen (testosterone) may predict properties of pre-speech babbling at five months. This study is the first attempt to investigate a possible correlation between sex hormones and infants' articulatory skills during the typical postnatal period of extended hormonal activity known as 'mini-puberty.' A hierarchical, multiple regression approach revealed a significant, robust positive relationship between 4-week concentrations of estradiol and individual articulatory skills. In contrast, testosterone concentrations at five months negatively correlated with articulatory skills at the same age in both boys and girls. Our findings reinforce the assumption of the importance of sex hormones for auditory-vocal development towards language in human infants.

Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial.

BACKGROUND: HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. METHODS: Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/µl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/µl. RESULTS: No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/µl compared to -37.42 ± 10.77 cells/µl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. CONCLUSIONS: This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT01299948.

Cost for physician-diagnosed influenza and influenza-like illnesses on primary care level in Germany--results of a database analysis from May 2010 to April 2012.

BACKGROUND: Seasonal influenza is one of the most significant infectious diseases in Germany; epidemic outbreaks occur every winter and cause substantial morbidity and mortality. However, published data from Germany on the current economic burden of influenza and the costs per episode are lacking. METHODS: A retrospective database analysis was conducted using a longitudinal electronic medical records database (IMS Disease Analyzer). Patients with influenza, diagnosed by German office-based physicians using ICD-10 J09-11 (International Classification of Diseases, 10(th) revision), who were observable in the database from 12 months before the index (diagnosis) date until 1 month afterwards, were included. The selection window, defined to cover two influenza seasons, was May 2010 to April 2012. Direct and indirect costs were evaluated from payer, patient and societal perspectives. Published unit costs and tariffs from Germany (2012) were used for the analysis. RESULTS: A total of 21,039 influenza-attributable episodes in 17,836 adults, managed by primary care physicians (PCP) and 7,107 episodes in 6,288 children, managed by pediatricians, were eligible for analysis. The mean (±Standard Deviation (SD)) age of the adults with at least one episode was 46 (±18) years and 7 (±4) years in the children. The presence of clinical risk factors was documented for 39% episodes in adults and 24% episodes in children, with the most common being cardiovascular diseases in adults (29%) and chronic respiratory diseases in children (23%). Complications and severe symptoms accompanied the influenza-attributable episode (adults: 37%, children: 54%), bronchitis (adults: 16%, children: 19%) and acute upper respiratory infection (adults: 15%, children: 21%) being the most frequent. From a societal perspective, the total average mean cost (±SD) per episode was €514 (±609) in adults, where work days lost were the main cost driver (82%), and €105 (±224) in children. Complications and severe symptoms increased the cost per episode versus episodes without by 1.7 times in adults (€684 (±713) vs. €413 (±510)) and nearly 3 times in children (€149 (±278) vs. €55 (±116)). CONCLUSIONS: Based on a large patient sample derived from representative PCP and pediatricians panels, our results demonstrate that seasonal influenza is associated with substantial clinical and economic burden in Germany.

Trabeculectomy versus canaloplasty (TVC study) in the treatment of patients with open-angle glaucoma: a prospective randomized clinical trial.

PURPOSE: To compare the outcomes of canaloplasty and trabeculectomy in open-angle glaucoma. METHODS: This prospective, randomized clinical trial included 62 patients who randomly received trabeculectomy (n = 32) or canaloplasty (n = 30) and were followed up prospectively for 2 years. Primary endpoint was complete (without medication) and qualified success (with or without medication) defined as an intraocular pressure (IOP) of ≤18 mmHg (definition 1) or IOP ≤21 mmHg and ≥20% IOP reduction (definition 2), IOP ≥5 mmHg, no vision loss and no further glaucoma surgery. Secondary endpoints were the absolute IOP reduction, visual acuity, medication, complications and second surgeries. RESULTS: Surgical treatment significantly reduced IOP in both groups (p < 0.001). Complete success was achieved in 74.2% and 39.1% (definition 1, p = 0.01), and 67.7% and 39.1% (definition 2, p = 0.04) after 2 years in the trabeculectomy and canaloplasty group, respectively. Mean absolute IOP reduction was 10.8 ± 6.9 mmHg in the trabeculectomy and 9.3 ± 5.7 mmHg in the canaloplasty group after 2 years (p = 0.47). Mean IOP was 11.5 ± 3.4 mmHg in the trabeculectomy and 14.4 ± 4.2 mmHg in the canaloplasty group after 2 years. Following trabeculectomy, complications were more frequent including hypotony (37.5%), choroidal detachment (12.5%) and elevated IOP (25.0%). CONCLUSIONS: Trabeculectomy is associated with a stronger IOP reduction and less need for medication at the cost of a higher rate of complications. If target pressure is attainable by moderate IOP reduction, canaloplasty may be considered for its relative ease of postoperative care and lack of complications.

Different duration strategies of perioperative antibiotic prophylaxis in adult patients undergoing cardiac surgery: an observational study.

BACKGROUND: All international guidelines recommend perioperative antibiotic prophylaxis (PAB) should be routinely administered to patients undergoing cardiac surgery. However, the duration of PAB is heterogeneous and controversial. METHODS: Between 01.01.2011 and 31.12.2011, 1096 consecutive cardiac surgery patients were assigned to one of two groups receiving PAB with a second-generation cephalosporin for either 56 h (group I) or 32 h (group II). Patients' characteristics, intraoperative data, and the in-hospital follow-up were analysed. Primary endpoint was the incidence of surgical site infection (deep and superficial sternal wound-, and vein harvesting site infection; DSWI/SSWI/VHSI). Secondary endpoints were the incidence of respiratory-, and urinary tract infection, as well as the mortality rate. RESULTS: 615/1096 patients (56,1%) were enrolled (group I: n = 283 versus group II: n = 332). There were no significant differences with regard to patient characteristics, comorbidities, and procedure-related variables. No statistically significant differences were demonstrated concerning primary and secondary endpoints. The incidence of DSWI/SSWI/VHSI were 4/283 (1,4%), 5/283 (1,7%), and 1/283 (0,3%) in group I versus 6/332 (1,8%), 9/332 (2,7%), and 3/332 (0,9%) in group II (p = 0,76/0,59/0,63). In univariate analyses female gender, age, peripheral arterial obstructive disease, operating-time, ICU-duration, transfusion, and respiratory insufficiency were determinants for nosocomial infections (all ≤ 0,05). Subgroup analyses of these high-risk patients did not show any differences between the two regimes (all ≥ 0,05). CONCLUSIONS: Reducing the duration of PAB from 56 h to 32 h in adult cardiac surgery patients was not associated with an increase of nosocomial infection rate, but contributes to reduce antibiotic resistance and health care costs.

Inner and outer central retinal findings after surgery for rhegmatogenous retinal detachment using different spectral-domain optical coherence tomography devices.

PURPOSE: The aim of the study was to analyse macular changes after rhegmatogenous retinal detachment (RRD) repair using spectral-domain optical coherence tomography (SD-OCT). METHODS: Forty eyes with macula-on and 27 eyes with macula-off RRD underwent scleral buckling or vitrectomy and were postoperatively imaged using 2 SD-OCT devices (Cirrus® HD-OCT, RTVue-100®). Measurement of total and inner macular thickness consisting of ganglion cell layer + inner plexiform layer (GCL-IPL) using Cirrus or retinal nerve fibre layer + ganglion cell layer + inner plexiform layer (RNFL-GCL-IPL) using RTVue was performed. Results of inner macular thickness were compared with image results of 40 healthy controls. Qualitative analysis of inner and outer retinal layers was additionally assessed. RESULTS: Measurement of overall retinal thickness within the 9 ETDRS sectors was highly correlated between both OCTs (Pearson's r, range 0.88-0.99; p < 0.001). Correlation of RNFL-GCL-IPL complex between OCTs was excellent in both surgery groups (Pearson's r, range 0.73-0.88; p < 0.001) and normal controls (Pearson's r, range 0.79-0.90; p < 0.001). The RNFL-GCL-IPL complex was thicker in both surgery groups compared to normal controls using Cirrus. Outer retinal findings of macula-off patients were seen in four eyes (14.8 %). Visual acuity (VA) significantly improved in both groups independent of preoperative VA or duration of symptoms. CONCLUSION: Agreement between both OCTs was excellent for overall and inner retinal thickness, although RTVue measured a thicker RNFL-GCL-IPL complex. Thinning of inner retinal layers as a potential cause of poor VA was rarely detected, possibly due to tractional changes at the vitreomacular interface. VA improved even in patients with macula-involving RRD.

4Flu - an individual based simulation tool to study the effects of quadrivalent vaccination on seasonal influenza in Germany.

BACKGROUND: Influenza vaccines contain Influenza A and B antigens and are adjusted annually to match the characteristics of circulating viruses. In Germany, Influenza B viruses belonged to the B/Yamagata lineage, but since 2001, the antigenically distinct B/Victoria lineage has been co-circulating. Trivalent influenza vaccines (TIV) contain antigens of the two A subtypes A(H3N2) and A(H1N1), yet of only one B lineage, resulting in frequent vaccine mismatches. Since 2012, the WHO has been recommending vaccine strains from both B lineages, paving the way for quadrivalent influenza vaccines (QIV). METHODS: Using an individual-based simulation tool, we simulate the concomitant transmission of four influenza strains, and compare the effects of TIV and QIV on the infection incidence. Individuals are connected in a dynamically evolving age-dependent contact network based on the POLYMOD matrix; their age-distribution reproduces German demographic data and predictions. The model considers maternal protection, boosting of existing immunity, loss of immunity, and cross-immunizing events between the B lineages. Calibration to the observed annual infection incidence of 10.6% among young adults yielded a basic reproduction number of 1.575. Vaccinations are performed annually in October and November, whereby coverage depends on the vaccinees' age, their risk status and previous vaccination status. New drift variants are introduced at random time points, leading to a sudden loss of protective immunity for part of the population and occasionally to reduced vaccine efficacy. Simulations run for 50 years, the first 30 of which are used for initialization. During the final 20 years, individuals receive TIV or QIV, using a mirrored simulation approach. RESULTS: Using QIV, the mean annual infection incidence can be reduced from 8,943,000 to 8,548,000, i.e. by 395,000 infections, preventing 11.2% of all Influenza B infections which still occur with TIV (95% CI: 10.7-11.8%). Using a lower B lineage cross protection than the baseline 60%, the number of Influenza B infections increases and the number additionally prevented by QIV can be 5.5 times as high. CONCLUSIONS: Vaccination with TIV substantially reduces the Influenza incidence compared to no vaccination. Depending on the assumed degree of B lineage cross protection, QIV further reduces Influenza B incidence by 11-33%.

Sex hormone influence on human infants' sound characteristics: melody in spontaneous crying.

The specific impact of sex hormones on brain development and acoustic communication is known from animal models. Sex steroid hormones secreted during early development play an essential role in hemispheric organization and the functional lateralization of the brain, e.g. language. In animals, these hormones are well-known regulators of vocal motor behaviour. Here, the association between melody properties of infants' sounds and serum concentrations of sex steroids was investigated. Spontaneous crying was sampled in 18 healthy infants, averaging two samples taken at four and eight weeks, respectively. Blood samples were taken within a day of the crying samples. The fundamental frequency contour (melody) was analysed quantitatively and the infants' frequency modulation skills expressed by a melody complexity index (MCI). These skills provide prosodic primitives for later language. A hierarchical, multiple regression approach revealed a significant, robust relationship between the individual MCIs and the unbound, bioactive fraction of oestradiol at four weeks as well as with the four-to-eight-week difference in androstenedione. No robust relationship was found between the MCI and testosterone. Our findings suggest that oestradiol may have effects on the development and function of the auditory-vocal system in human infants that are as powerful as those in vocal-learning animals.

Development and validation of a fully GMP-compliant production process of autologous, tumor-lysate-pulsed dendritic cells.

BACKGROUND AND AIMS: One of the major challenges of dendritic cell (DC) vaccination is the establishment of harmonized DC production protocols. Here, we report the transfer and validation of a successfully used open DC manufacturing method into a closed system, good manufacturing practice (GMP)-compatible protocol. METHODS: All production steps (lysate generation, monocyte selection, DC culture and cryopreservation) were standardized and validated. RESULTS: Tumor lysate was characterized by histology, mechanically homogenized and avitalized. This preparation yielded a median of 58 ± 21 µg protein per milligram of tumor tissue. Avitality was determined by trypan blue staining and confirmed in an adenosine triphosphate release assay. Patient monocytes were isolated by elutriation or CD14 selection, which yielded equivalent results. DCs were subsequently differentiated in Teflon bags for an optimum of 7 days in CellGro medium supplemented with interleukin (IL)-4 and granulocyte macrophage colony stimulating factor and then matured for 48 h in tumor necrosis factor-α and IL-1ß after pulsing with tumor lysate. This protocol resulted in robust and reproducible upregulation of DC maturation markers such as cluster of differentiation (CD)80, CD83, CD86, human leukocyte antigen-DR and DC-SIGN. Functionality of these DCs was shown by directed migration toward C-C motif chemokine ligand 19/21, positive T-cell stimulatory capacity and the ability to prime antigen-specific T cells from naive CD8(+) T cells. Phenotype stability, vitality and functionality of DCs after cryopreservation, thawing and washing showed no significant loss of function. Comparison of clinical data from 146 patients having received vaccinations with plate-adherence versus GMP-grade DCs showed no inferiority of the latter. CONCLUSIONS: Our robust, validated and approved protocol for DC manufacturing forms the basis for a harmonized procedure to produce cancer vaccines, which paves the way for larger multi-center clinical trials.

Non-steroidal anti-inflammatory drug hypersensitivity: association with elevated basal serum tryptase?

BACKGROUND: It is hypothesized that because of higher mast cell numbers and mediator release, mastocytosis predisposes patients for systemic immediate-type hypersensitivity reactions to certain drugs including non-steroidal anti-inflammatory drugs (NSAID). OBJECTIVE: To clarify whether patients with NSAID hypersensitivity show increased basal serum tryptase levels as sign for underlying mast cell disease. METHODS: As part of our allergy work-up, basal serum tryptase levels were determined in all patients with a diagnosis of NSAID hypersensitivity and the severity of the reaction was graded. Patients with confirmed IgE-mediated hymenoptera venom allergy served as a comparison group. RESULTS: Out of 284 patients with NSAID hypersensitivity, 26 were identified with basal serum tryptase > 10.0 ng/mL (9.2%). In contrast, significantly (P = .004) more hymenoptera venom allergic patients had elevated tryptase > 10.0 ng/mL (83 out of 484; 17.1%). Basal tryptase > 20.0 ng/mL was indicative for severe anaphylaxis only in venom allergic subjects (29 patients; 4x grade 2 and 25x grade 3 anaphylaxis), but not in NSAID hypersensitive patients (6 patients; 4x grade 1, 2x grade 2). CONCLUSIONS: In contrast to hymenoptera venom allergy, NSAID hypersensitivity do not seem to be associated with elevated basal serum tryptase levels and levels > 20 ng/mL were not related to increased severity of the clinical reaction. This suggests that mastocytosis patients may be treated with NSAID without special precautions.

Single venom-based immunotherapy effectively protects patients with double positive tests to honey bee and Vespula venom.

BACKGROUND: Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms "double sensitization" or "double positivity" cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients. OBJECTIVE: We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients. METHODS: Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests. RESULTS: Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15). CONCLUSIONS: Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the culprit stinging insect.

Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals.

Dysfunction of dopaminergic neurotransmission has been implicated in HIV infection. We showed previously increased dopamine (DA) levels in CSF of therapy-naïve HIV patients and an inverse correlation between CSF DA and CD4 counts in the periphery, suggesting adverse effects of high levels of DA on HIV infection. In the current study including a total of 167 HIV-positive and negative donors from Germany and South Africa (SA), we investigated the mechanistic background for the increase of CSF DA in HIV individuals. Interestingly, we found that the DAT 10/10-repeat allele is present more frequently within HIV individuals than in uninfected subjects. Logistic regression analysis adjusted for gender and ethnicity showed an odds ratio for HIV infection in DAT 10/10 allele carriers of 3.93 (95% CI 1.72-8.96; p = 0.001, Fishers exact test). 42.6% HIV-infected patients harbored the DAT 10/10 allele compared to only 10.5% uninfected DAT 10/10 carriers in SA (odds ratio 6.31), whereas 68.1 versus 40.9%, respectively, in Germany (odds ratio 3.08). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT genotypes. These intriguing and novel findings show the mutual interaction between DA and HIV, suggesting caution in the interpretation of CNS DA alterations in HIV infection solely as a secondary phenomenon to the virus and open the door for larger studies investigating consequences of the DAT functional polymorphism on HIV epidemiology and progression of disease.

Chlamydia trachomatis infection induces replication of latent HHV-6.

Human herpesvirus-6 (HHV-6) exists in latent form either as a nuclear episome or integrated into human chromosomes in more than 90% of healthy individuals without causing clinical symptoms. Immunosuppression and stress conditions can reactivate HHV-6 replication, associated with clinical complications and even death. We have previously shown that co-infection of Chlamydia trachomatis and HHV-6 promotes chlamydial persistence and increases viral uptake in an in vitro cell culture model. Here we investigated C. trachomatis-induced HHV-6 activation in cell lines and fresh blood samples from patients having Chromosomally integrated HHV-6 (CiHHV-6). We observed activation of latent HHV-6 DNA replication in CiHHV-6 cell lines and fresh blood cells without formation of viral particles. Interestingly, we detected HHV-6 DNA in blood as well as cervical swabs from C. trachomatis-infected women. Low virus titers correlated with high C. trachomatis load and vice versa, demonstrating a potentially significant interaction of these pathogens in blood cells and in the cervix of infected patients. Our data suggest a thus far underestimated interference of HHV-6 and C. trachomatis with a likely impact on the disease outcome as consequence of co-infection.

Comparison of the Airtraq and the Macintosh laryngoscope for double-lumen tube intubation: a randomised clinical trial.

CONTEXT: The Airtraq is a disposable optical laryngoscope that is available in a double-lumen tube version. Inserting a double-lumen tube is generally more difficult compared to conventional endotracheal intubation, mainly due to its configuration. OBJECTIVE: The aim of this study was to compare the Airtraq with the Macintosh laryngoscope for intubation with a double-lumen tube in patients undergoing elective thoracic surgery. The main outcome was time needed for successful intubation. DESIGN: Prospective, randomised clinical trial. SETTING: A single centre, University Hospital of Würzburg, Germany, between July 2009 and June 2011. PATIENTS: After a scout laryngoscopy with a Macintosh laryngoscope, 60 adult patients were intubated by an anaesthesiologist with either an Airtraq (n = 30) or a Macintosh laryngoscope (n = 30). MAIN OUTCOME MEASURES: The time needed for correct intubation, checked by flexible bronchoscopy, was recorded. The intubation difficulty scale (IDS) and Cormack and Lehane grade were noted. Haemodynamic variables and any evidence of oropharyngeal trauma were documented as well as postoperative sore throat, hoarseness and dysphagia. RESULTS: The mean time needed for correct intubation was 20.1 ± 16.5 s in the Airtraq group and 17.5 ± 10 s in the Macintosh group (P = 0.86). All intubations in both groups had an IDS less than 4. The Cormack and Lehane grade was I in all 30 patients in the Airtraq group; in the Macintosh group, it was I and II in 17 and 13 patients, respectively. The incidence of hoarseness was significantly higher in the Airtraq group 24 h postoperatively (P = 0.01). CONCLUSION: There was no significant difference between the Airtraq and the Macintosh laryngoscopes regarding the time needed to insert a double-lumen tube during elective thoracic surgery. Only subtle enhancement of visualisation and a higher incidence of hoarseness were observed in the Airtraq group. The Airtraq device did not result in superior patient safety in this setting.

The predictive value of multiple electrode platelet aggregometry (multiplate) in adult cardiac surgery.

BACKGROUND: The purpose of this retrospective observational study is to analyze the value of multiple electrode platelet aggregometry (Multiplate analyzer, Verum Diagnostica, Munich) as a point-of-care (POC) device in adult cardiac surgical patients. METHODS: Two hundred and twenty-three cardiac surgical patients were analyzed preoperatively and postoperatively with multiple electrode platelet aggregometry by stimulation ADPtest, ASPItest, and TRAPtest. End points were postoperative bleeding, need for reexploration, and perioperative transfusions requirements. Furthermore, a literature survey using the key phrases "platelet function" and "cardiac surgery" was performed. RESULTS: When comparing patients with normal Multiplate test results concerning end points, patients with pathological ADPtest (n = 140) needed significant more platelet concentrates (PCs) (p = 0.009), patients with pathological ASPItest (n = 175) did not show any significant differences, and patients with pathological TRAPtest (n = 139) needed more red blood cells (p = 0.008) and PCs (p = 0.02). The literature survey showed 208 hits, spanning the publication years 2002 to 2012 resulted in 123 hits. CONCLUSIONS: The ADPtest and the TRAPtest significantly predict the requirement of perioperative blood transfusion. Therefore, multiple electrode platelet aggregometry is beneficial for POC testing in cardiac surgical patients. Prospective, randomized, and controlled clinical studies are rare.

Single-port laparoscopic cholecystectomy versus standard multiport laparoscopic cholecystectomy: a case-control study comparing the long-term quality of life and body image.

PURPOSE: To study the postoperative quality of life and body image of patients who underwent either single-port cholecystectomy (SPC) or standard multiport laparoscopic cholecystectomy (SMLC) in a long-term assessment. METHODS: Fifty patients who underwent SPC using the reusable X-Cone™ Laparoscopic Device were compared with a matched group (age, sex, body mass index) of 50 patients after SMLC. The health-related quality of life (HRQOL) and body image at 17 months postoperatively (median, range 9-23) was analysed by means of the Short-Form 12 Health Survey and the Body Image Questionnaire, respectively. RESULTS: Both patient groups had comparable baseline characteristics, clinical courses, and postoperative complication rates. SPC patients were significantly more satisfied with the cosmetic result of their scar at 17 months postoperatively, in comparison to SMLC patients (cosmetic scale: 22.6 ± 2.8 vs. 19.5 ± 3.7, p < 0.001). However, the HRQOL did not differ between the SPC and SMLC patients (physical component scale: 50.0 ± 8.9 vs. 48.8 ± 9.4, p = 0.48; mental component scale: 53.8 ± 6.5 vs. 51.3 ± 8.5, p = 0.10). CONCLUSION: Although the overall postoperative HRQOL was comparable, this study suggests that the cosmetic result of SPC after complete wound healing is superior to the standard multiport laparoscopic procedure.