[SARS-CoV-2-associated deaths in adult persons up to 50 years of age]. / SARS-CoV-2-assoziierte Todesfälle von erwachsenen Personen bis 50 Jahre: Eine retrospektive Auswertung der COVID-19-assoziierten Todesfälle im Jahr 2020 im Institut für Rechtsmedizin Hamburg, Deutschland.

INTRODUCTION: Several evaluations of deaths in persons of advanced age associated with SARS-CoV­2 can be found in the international literature. The aim of this work was the evaluation of deaths associated with SARS-CoV­2 of persons of younger or middle age (up to 50 years) at the Institute of Legal Medicine in Hamburg, Germany, with presentation of frequency, comorbidities and disease courses. MATERIAL AND METHODS: A total of 735 SARS-CoV-2-associated cases of decedents with registered addresses in Hamburg were evaluated in 2020 at the Institute of Legal Medicine in Hamburg, Germany, using various examination methods. The selection and performance of the respective methods was based on the consent given by the relatives. In addition, more autopsies of decedents with a registered address outside Hamburg and positive SARS-CoV­2 detection were performed. RESULTS AND CONCLUSION: Of the 735 decedents 9 with a registered Hamburg address and 3 of the deaths studied with an external registered address (n = 12; 7 men and 5 women) were aged 50 years or younger, with an average age of 39.8 years. Essentially, there were cardiovascular, neurological, and malignant pre-existing diseases, as well as obesity. The SARS-CoV­2 was detected post-mortem for the first time in two cases; these were found to have a virus-independent cause of death. Of the individuals 7 died from COVID-19 pneumonia, 3 individuals from the consequences of the necessary intensive medical treatment.Several studies have demonstrated an association between obesity and severe SARS-CoV-2-related disease progression, particularly in younger patients and this was confirmed in the legal medicine study population.

[Dynamic contrast-enhanced MRI of the prostate: comparison of two different post-processing algorithms]. / Dynamische kontrastmittelunterstützte MRT der Prostata: Vergleich von zwei Auswerteverfahren.

PURPOSE: To evaluate the usefulness of a commercially available post-processing software tool for detecting prostate cancer on dynamic contrast-enhanced magnetic resonance imaging (MRI) and to compare the results to those obtained with a custom-made post-processing algorithm already tested under clinical conditions. MATERIALS AND METHODS: Forty-eight patients with proven prostate cancer were examined by standard MRI supplemented by dynamic contrast-enhanced dual susceptibility contrast (DCE-DSC) MRI prior to prostatectomy. A custom-made post-processing algorithm was used to analyze the MRI data sets and the results were compared to those obtained using a post-processing algorithm from In vivo Corporation (Dyna CAD for Prostate) applied to dynamic T 1-weighted images. Histology was used as the gold standard. RESULTS: The sensitivity for prostate cancer detection was 78 % for the custom-made algorithm and 60 % for the commercial algorithm and the specificity was 79 % and 82 %, respectively. The accuracy was 79 % for our algorithm and 77.5 % for the commercial software tool. The chi-square test (McNemar-Bowker test) yielded no significant differences between the two tools (p = 0.06). CONCLUSION: The two investigated post-processing algorithms did not differ in terms of prostate cancer detection. The commercially available software tool allows reliable and fast analysis of dynamic contrast-enhanced MRI for the detection of prostate cancer.

Barrier function of the gut and multiple organ dysfunction after cardiac surgery.

We studied the influence of sequential involvement of the gastrointestinal (GI) tract on the development of multiple organ dysfunction (MOD) after cardiopulmonary bypass (CPB). One hundred and forty-six patients undergoing elective cardiac surgery were included in this prospective observational study. Standardized oral inert-sugar tests (sucrose, lactulose, mannitol, sucralose) were performed before and after CPB in different patients. Enzyme-linked immunosorbent assay of plasma levels of endotoxin core antibodies (EndoCAb) were performed peri-operatively. The functional mucosal surface was calculated from the amount of mannitol absorbed from the GI tract. Lower urine concentrations of absorbed mannitol were observed pre-operatively in patients developing MOD. In binary logistic regression this was an independent parameter. Decreased plasma concentrations of EndoCAb after surgery were seen in every patient, but were more significant in patients developing MOD. A reduced pre-operative functional mucosal surface may predict the early occurrence of MOD after surgery.

Modeling material saturation effects in microholographic recording.

Microholographic data storage system model is presented that includes non-linear and non-local behavior of the storage material for accurate simulation of the system and optimization of the writing process. For the description of the photopolymer material a diffusion based nonlocal material model is used. The diffusion equation is solved numerically and the modulation of the dielectric constant is calculated. Diffraction efficiency of simulated microholograms and measurements were compared, and they show good agreement.

Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria.

Genetic host factors play a substantial role in susceptibility to and severity of malaria, which continues to cause at least one million deaths per year. Recently, members of the toll-like receptor (TLR) family have been shown to be involved in recognition of the etiologic organism Plasmodium falciparum: The glycosylphosphatidylinisitol anchor induces signaling in host cells via TLR-2 and -4, while hemozoin-induced immune activation involves TLR-9. Binding of microbial ligands to the respective TLRs triggers the release of pro-inflammatory cytokines via the TLR/IL-1 receptor (TIR) domain and may contribute to the host response, including pro-inflammatory cytokine induction and malarial fever. In a case-control study among 870 Ghanaian children, we examined the influence of TLR-2, -4, and -9 polymorphisms in susceptibility to severe malaria. TLR-2 variants common in Caucasians and Asians were completely absent. However, we found a new, rare mutation (Leu658Pro), which impairs signaling via TLR-2. We failed to detect any polymorphisms within the TLR-9/interleukin-1 receptor domain. Two frequent TLR-9 promoter polymorphisms did not show a clear association with malaria severity. In contrast, the TLR-4-Asp299Gly variant occurred at a high rate of 17.6% in healthy controls, and was even more frequent in severe malaria patients (24.1%, p<0.05). Likewise, TLR-4-Thr399Ile was seen in 2.4% of healthy children and in 6.2% of patients (p=0.02). TLR-4-Asp299Gly and TLR-4-Thr399Ile conferred an 1.5- and 2.6-fold increased risk of severe malaria, respectively. These findings suggest TLR4-mediated responses to malaria in vivo and TLR-4 polymorphisms to be associated with disease manifestation. However some gray areas also suggest the scope for further improvements.

Economic and social impacts of La Crosse encephalitis in western North Carolina.

La Crosse encephalitis (LACE), a human illness caused by a mosquito-transmitted virus, is endemic in western North Carolina. To assess the economic and social impacts of the illness, 25 serologically confirmed LACE case patients and/or families were interviewed to obtain information on the economic costs and social burden of the disease. The total direct and indirect medical costs associated with LACE over 89.6 life years accumulated from the onset of illness to the date of interview for 24 patients with frank encephalitis totaled dollar 791,374 (range = dollar 7,521-175,586), with a mean +/- SD per patient cost of dollar 32,974 +/- dollar 34,793. The projected cost of a case with lifelong neurologic sequelae ranged from dollar 48,775 to dollar 3,090,798 (n = 5). For the 25 LACE patients, 55.15 (54.83%) of the 100.59 cumulative life years (CLYs) were impaired to some degree. Disability adjusted life years (DALYs) were calculated to measure the productive life years lost to LACE. Approximately 13.00 DALYs were accumulated over 100.59 CLYs of study. Projected DALYs for case patients (n = 5) with lifelong neurologic sequelae ranged from 12.90 to 72.37 DALYs. An Impact of La Crosse Encephalitis Survey (ILCES) was used to measure the social impact of LACE over time for case patients and their families. The ILCES scores demonstrated that the majority of the social burden of the illness is borne by the five patients with lifelong neurologic sequelae. The socioeconomic burden resulting from LACE is substantial, which highlights the importance of the illness in western North Carolina, as well as the need for active surveillance, reporting, and prevention programs for the infection.

Nurse practitioner use of computer technologies in practice.

A study was undertaken to determine computer use by nurse practitioners in public clinics, private practice, health maintenance organizations, and other settings in the greater San Francisco Bay Area. The descriptive research used a survey design. Subjects were 200 nurse practitioners. The survey instrument was developed by the researcher. Of the 104 respondents, 86 (83%) used computers at work. "Obtaining client records from other agencies or departments" was rated the most useful computer application for improving client care. "Internet searches" was rated the next most useful computer application; "entering client record information" was rated the third most useful. Use of computer applications varied by practice setting. Only 7 (25%) nurse practitioners in private practice accessed client records from other agencies, as did 17 (57%) in public clinics, and nearly all, 29 (94%), in HMOs. The research demonstrated that nurse practitioners underused computer applications that would improve client care in their practice.

HIV-related nontuberculous mycobacterial infection: incidence, survival analysis and associated risk factors.

To evaluate the incidence and survival time for AIDS-patients affected by different stages of nontuberculous mycobacterial (NTM) infection we performed a retrospective study. Data of 1540 hospitalised AIDS-patients was analyzed with respect to survival time and incidence rates. The overall incidence rate of NTM following AIDS was 16.6/100 person-years (PY), with an increase from 12.1/100PY (1987-1990) to 18.9/100PY (1991-1994). Antiretroviral therapy (ART) and toxoplasmosis prophylaxis reduced the risk of NTM disease whereas CD4 cells <40/ microl at time of the first AIDS defining illness led to a 2.5 fold higher risk. Pneumocystis carinii pneumonia (PCP), wasting syndrome and PCP prophylaxis increased the risk of progression from colonization to dissemination. Cryptococcus neoformans infection, wasting syndrome, PCP prophylaxis and CD4 cells <40/ microl were linked to immediate NTM dissemination. Though the incidence of NTM dissemination increased by the factor 1.56 in 1991-1994, survival did not differ between patients with and without NTM infection.

Space-time mixture modelling of public health data.

This paper aims to enlarge the usual scope of disease mapping by means of dynamic mixtures (DMDM) in case a time component is involved in the data. A special mixture model is suggested which looks for space-time components (clusters) simultaneously. The idea is illustrated using data on female lung cancer from the East German cancer registry for 1960-1989. The conventional mixed Poisson regression model is used as a third model for comparison. The models are discussed in terms of their benefits, difficulties and ease in interpretation, as well as their statistical meaning. Some ideas on evaluation of these models are also included.

Effects of anticoagulant, processing delay, and assay method (branched DNA versus reverse transcriptase PCR) on measurement of human immunodeficiency virus type 1 RNA levels in plasma.

We conducted two studies to determine the potential influence of delays in blood processing, type of anticoagulant, and assay method on human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma. The first was an experimental study in which heparin- and EDTA-anticoagulated blood samples were collected from 101 HIV-positive individuals and processed to plasma after delays of 2, 6, and 18 h. HIV-1 RNA levels in each sample were then measured by both branched-DNA (bDNA) and reverse transcriptase PCR (RT-PCR) assays. Compared to samples processed within 2 h, the loss (decay) of HIV-1 RNA in heparinized blood was significant (P < 0.05) but small after 6 h (bDNA assay, -0.12 log(10) copies/ml; RT-PCR, -0.05 log(10) copies/ml) and after 18 h (bDNA assay, -0.27 log(10) copies/ml; RT-PCR, -0.15 log(10) copies/ml). Decay in EDTA-anticoagulated blood was not significant after 6 h (bDNA assay, -0.002 log(10) copies/ml; RT-PCR, -0.02 log(10) copies/ml), but it was after 18 h (bDNA assay, -0.09 log(10) copies/ml; RT-PCR, -0.09 log(10) copies/ml). Only 4% of samples processed after 6 h lost more than 50% (>/=0.3 log(10) copies/ml) of the HIV-1 RNA, regardless of the anticoagulant or the assay that was used. The second study compared HIV-1 RNA levels in samples from the Multicenter AIDS Cohort Study (MACS; samples were collected in heparin-containing tubes in 1985, had a 6-h average processing delay, and were assayed by bDNA assay) and the British Columbia Drug Treatment Program (BCDTP) (collected in EDTA- or acid citrate dextrose-containing tubes in 1996 and 1997, had a 2-h maximum processing delay, and were assayed by RT-PCR). HIV-1 RNA levels in samples from the two cohorts were not significantly different after adjusting for CD4(+)-cell count and converting bDNA assay values to those corresponding to the RT-PCR results. In summary, the decay of HIV-1 RNA measured in heparinized blood after 6 h was small (-0.05 to -0.12 log(10) copies/ml), and the minor impact of this decay on HIV-1 RNA concentrations in archived plasma samples of the MACS was confirmed by the similarity of CD4(+)-cell counts and assay-adjusted HIV-1 RNA concentrations in the MACS and BCDTP.

The relationship between alcohol consumption, health indicators and mortality in the German population.

BACKGROUND: The patterns of total alcohol, beer and wine consumption were evaluated in the German National Health Surveys. The impact of these habits on cardiovascular and all-cause mortality as well as cardiovascular risk factors and liver disease parameters was estimated. METHODS: Independent representative samples of the German population (15,400 people), and regional samples of the Berlin-Spandau population (2,370 in total), aged 25-69 years, were analysed. The amount and frequency of alcohol consumption was assessed with standardized questionnaires. Biochemical analyses included serum lipids and gamma-glutamyl-transpeptidase (Gamma GT). Multiple analyses of variance were used to determine the relationship between alcohol intake and biochemical parameters. A mortality follow-up of about 7 years was conducted for the Berlin-Spandau population. Proportional hazard models were used to estimate hazard ratios (HR) for all-cause and cardiovascular mortality. RESULTS: Over 80% of men and 55% of women in Germany drink alcohol on a regular base. The majority of the consumers (65% of men, 87% of women) are light (1-20 g/day) or moderate (21-40 g/day) drinkers. Higher serum high density lipoprotein (HDL)-cholesterol and Gamma GT levels were observed with increasing alcohol intake. In light and moderate drinkers no significant relationship was seen with non-HDL-cholesterol, triglycerides, blood pressure and body mass index, compared to teetotallers. Men who consumed 1-20 g alcohol/day had a significantly lower all-cause and cardiovascular mortality. As compared to nondrinkers, the risk was almost 50% lower. CONCLUSION: The results suggest that light (and possibly moderate) alcohol consumption reduces the risk of cardiovascular and total mortality risk and is favourably related to HDL-cholesterol.

Survival of vancomycin-resistant and vancomycin-susceptible enterococci on dry surfaces.

We compared the abilities of Enterococcus faecium strains (three vancomycin-resistant enterococci [VRE] and five vancomycin-susceptible enterococci [VSE]) and Enterococcus faecalis strains (one VRE and 10 VSE) to survive under dry conditions. Bacterial suspensions of the strains were inoculated onto polyvinyl chloride and stored under defined conditions for up to 16 weeks. All strains survived for at least 1 week, and two strains survived for 4 months. A statistical model was used to distribute the 19 resulting survival curves between two types of survival curves. The type of survival curve was not associated with the species (E. faecalis versus E. faecium), the source of isolation (patient versus environment), or the susceptibility to vancomycin (VRE versus VSE). Resistance to dry conditions may promote the transmissibility of a strain, but VRE have no advantages over VSE with respect to their ability to survive under dry conditions.

Recent developments in computer-assisted analysis of mixtures.

This paper reviews recent developments in the area of computer-assisted analysis of mixture distributions (C.A.MAN). Given a biometric situation of interest in which, under homogeneity assumptions, a certain parametric density occurs, such as the Poisson, the binomial, the geometric, the normal, and so forth, then it is argued that this situation can easily be enlarged to allow a variation of the scalar parameter in the population. This situation is called unobserved heterogeneity. This naturally leads to a specific form of nonparametric mixture distribution that can then be assumed to be the standard model in the biometric application of interest (since it also incorporates the homogeneous situations as a special case). Besides developments in theory and algorithms, the work focuses on developments in biometric applications such as meta-analysis, fertility studies, estimation of prevalence under clustering, and estimation of the distribution function of survival time under interval censoring. The approach is nonparametric for the mixing distribution, including leaving the number of components (subpopulations) of the mixing distribution unknown.

Survival of Acinetobacter baumannii on dry surfaces.

Acinetobacter spp. have frequently been reported to be the causative agents of hospital outbreaks. The circumstances of some outbreaks demonstrated the long survival of Acinetobacter in a dry, inanimate environment. In laboratory experiments, we compared the abilities of five Acinetobacter baumannii strains, three Acinetobacter sp. strains from the American Type Culture Collection (ATCC), one Escherichia coli ATCC strain, and one Enterococcus faecium ATCC strain to survive under dry conditions. Bacterial solutions of the 10 strains were inoculated onto four different material samples (ceramic, polyvinyl chloride, rubber, and stainless steel) and stored under defined conditions. We investigated the bacterial counts of the material samples immediately after inoculation, after drying, and after 4 h, 1 day, and 1, 2, 4, 8, and 16 weeks of storage. A statistical model was used to distribute the 40 resulting curves among four types of survival curves. The type of survival curve was significantly associated with the bacterial strain but not with the material. The ability of the A. baumannii strains to survive under dry conditions varied greatly and correlated well with the source of the strain. Strains isolated from dry sources survived better than those isolated from wet sources. An outbreak strain that had caused hospital-acquired respiratory tract infections survived better than the strains from wet sources, but not as well as strains from dry sources. Resistance to dry conditions may promote the transmissibility of a strain, but it is not sufficient to make a strain an epidemic one. However, in the case of an outbreak, sources of Acinetobacter must be expected in the dry environment.

Impact of biological factors on the interpretation of bovine trypanosomosis serology.

A total of 457 cattle from dairy farms in Mukono County, Uganda, were investigated for Trypanosoma antibodies by ELISA. The objective of the study was to identify explanatory covariate factors for seropositivity among nine farm-specific and four animal-specific variables. We used logistic regression models for parasitological and serological outcome variables and then compared the adjusted odds ratios for explanatory factors between the models. Age is positively correlated with seropositivity but not with the detection of the parasite. Therefore, age group-specific cut-off values were established using mixture-distribution analysis. This procedure, as well as a mixture-distribution-derived cut-off value for the total sample, resulted in a greater relative efficiency of the ELISA as compared to conventional interpretation (cut-off value defined using non-exposed negative controls). The relevance of age and other biological factors for the serological status is briefly discussed.

Co-infection by Cryptococcus neoformans and Mycobacterium avium intracellulare in AIDS.

In the observation of various opportunistic pathogens in HIV-positive persons, co-infection by Cryptococcus neoformans together with Mycobacterium avium intracellulare was found if there was a CD4 lymphocyte count as low as 3-20 microl. In 1540 HIV-positive patients under treatment at a Berlin hospital (Auguste-Viktoria-Krankenhaus) during 1985-1994, all AIDS-relevant diseases were examined in a multivariate analysis as variables of influence on the manifestation of a systemic Mycobacterium avium complex (MAC) infection. The analysis involved data on 36 cases of cryptococcosis and 202 cases with a typical clinical course in whom MAC had been detected at sterile body sites. As significant and independent factors of influence, the following were identified: C. neoformans infection, wasting syndrome, lower age, low CD4 lymphocyte count and preceding Pneumocystis carinii pneumonia (PcP) prophylaxis. Cryptococcosis ranged first with an odds ratio of 2.75. The concomitant manifestation of cryptococcosis and systemic MAC infection in six patients is shown. Because both opportunists, C. neoformans and avian mycobacteria, may have their common habitat in droppings of defined species of pet birds, a common source of infection deserves further clinical and epidemiological attention.

Co-infection by Cryptococcus neoformans and Mycobacterium avium intracellulare in AIDS. Clinical and epidemiological aspects.

In the observation of various opportunistic pathogens in HIV-positive persons, co-infection by Cryptococcus neoformans together with Mycobacterium avium intracellulare was found if there was a CD4 lymphocyte count as low as 3-20/microliters. In 1540 HIV-positive patients under treatment at a Berlin hospital (Auguste-Viktoria-Krankenhaus) during 1985-1994, all AIDS-relevant diseases were examined in a multivariate analysis as variables of influence on the manifestation of a systemic Mycobacterium avium complex (MAC) infection. The analysis involved data on 36 cases of cryptococcosis and 202 cases with a typical clinical course in whom MAC had been detected at sterile body sites. As significant and independent factors of influence, the following were identified: C. neoformans infection, wasting syndrome, lower age, low CD4 lymphocyte count and preceding Pneumocystis carinii pneumonia (PcP) prophylaxis. Cryptococcosis ranged first with an ods ratio of 2.75. The concomitant manifestation of cryptococcosis and systemic MAC infection in six patients is shown. Because both opportunists, C. neoformans and avian mycobacteria, may have their common habitat in droppings of defined species of pet birds, a common source of infection deserves further clinical and epidemiological attention.

Covariate adjusted mixture models and disease mapping with the program DismapWin.

The analysis and recognition of disease clustering in space and its representation on a map is an important problem in epidemiology. An approach using mixture models to identify spatial heterogeneity in disease risk and map construction within an empirical Bayes framework is described. Once heterogeneity is detected, the question arises as how explanatory variables could be included in the model. A mixed Poisson regression approach to include covariates is presented. The methods are illustrated using data for tuberculosis from Berlin in 1991.