Prevalence of pre-operative anaemia in surgical patients: a retrospective, observational, multicentre study in Germany.

Anaemia is a risk factor for several adverse postoperative outcomes. Detailed data about the prevalence of anaemia are not available over a long time-period in Germany. In this retrospective, observational, multicentre study, patients undergoing surgery in March in 2007, 2012, 2015, 2017 and 2019 were studied. The primary objective was the prevalence of anaemia at hospital admission. The secondary objectives were the association between anaemia and the number of units of red blood cells transfused, length of hospital stay and in-hospital mortality. A total of 23,836 patients were included from eight centres. The prevalence of pre-operative anaemia in patients aged ≥ 18 years decreased slightly from 37% in 2007 to 32.5% in 2019 (p = 0.01) and increased in patients aged ≤ 18 years from 18.8% in 2007 to 26.4% in 2019 (p > 0.001). The total amount of blood administered per 1000 patients decreased from 671.2 units in 2007 to 289.0 units in 2019. Transfusion rates in anaemic patients declined from 33.8% in 2007 to 19.1% in 2019 (p < 0.001) and in non-anaemic patients from 8.4% in 2007 to 3.4% in 2019 (p < 0.001). Overall, the mortality rate remained constant over the years: 2.9% in 2007, 2.1% in 2012, 2.5% in 2015, 1.9% in 2017 and 2.5% in 2019. In the presence of anaemia, mortality was significantly increased compared with patients without anaemia (OR 5.27 (95%CI 4.13-6.77); p < 0.001). Red blood cell transfusion was associated with an increased risk of mortality (OR 14.98 (95%CI 11.83-19.03); p < 0.001). Using multivariable linear regression analysis with fixed effects, we found that pre-operative anaemia (OR 2.08 (95%CI 1.42-3.05); p < 0.001) and red blood cell transfusion (OR 4.29 (95%CI 3.09-5.94); p < 0.001) were predictors of mortality but not length of stay (0.99 (95%CI 0.98-1.00) days; p = 0.12) and analysed years (2007 vs. 2019: OR 1.49 (95%CI 0.86-2.69); p = 0.07). Pre-operative anaemia affects more than 30% of surgical patients in Germany and multidisciplinary action is urgently required to reduce adverse outcomes.

Efficacy, acceptability, and tolerability of all available treatments for insomnia in the elderly: a systematic review and network meta-analysis.

OBJECTIVES: Symptoms of insomnia are highly prevalent in the elderly. A significant number of pharmacological and non-pharmacological interventions exist, but, up-to-date, their comparative efficacy and safety has not been sufficiently assessed. METHODS: We integrated the randomized evidence from every available treatment for insomnia in the elderly (>65 years) by performing a network meta-analysis. Several electronic databases were searched up to May 25, 2019. The two primary outcomes were total sleep time and sleep quality. Data for other 6 efficacy and 8 safety outcomes were also analyzed. RESULTS: Fifty-three RCTs with 6832 participants (75 years old on average) were included, 43 of which examined the efficacy of one or more drugs. Ten RCTs examined the efficacy of non-pharmacological interventions and were evaluated only with pairwise meta-analyses because they were disconnected from the network. The overall confidence in the evidence was very low primarily due to the small amount of data per comparison and their sparse connectedness. Several benzodiazepines, antidepressants, and z-drugs performed better in both primary outcomes, but few comparisons had data from more than one trial. The limited evidence on non-pharmacological interventions suggested that acupressure, auricular acupuncture, mindfulness-based stress reduction program, and tart cherry juice were better than their control interventions. Regarding safety, no clear differences were detected among interventions due to large uncertainty. CONCLUSIONS: Insufficient evidence exists on which intervention is more efficacious for elderly patients with insomnia. More RCTs, with longer duration, making more direct interventions among active treatments and presenting more outcomes are urgently needed.

Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10-3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.

Alcohol consumption after laryngectomy.

OBJECTIVE: The aim of the study was the analysis of drinking behaviour in laryngectomised patients and its concomitants in quality of life and mental health. STUDY DESIGN: Multi-centered cross-sectional study. PARTICIPANTS AND SETTING: Two hundred and twenty-five laryngectomised patients were asked to participate in the study. One hundred and seventy nine patients (80%) were interviewed after laryngectomy at six different ENT clinics in Germany. MAIN OUTCOME MEASURES: 'Questionnaire of Health Behaviour' (FEG), 'Short Questionnaire of Alcohol Risk', Hospital Anxiety and Depression Scale (HADS), Hornheider Questionnaire (HFB), Visual Analogue Scales (VAS) and the Quality of Life Questionnaires of the European Organization of Research and Treatment of Cancer (EORTC) (EORTC QLQ-C30, EORTC QLQ-H & N35). RESULTS: Alcohol dependence was found in 7% of the patients. Half of the respondents showed a constant consumption of alcohol with 6% of the patients who wanted to change their consumption. Patients with alcohol dependence indicated in comparison with non-dependent persons increased anxiety (p = 0.03), problems in coping with illness (p = 0.03), increased psychosocial care needs (p = 0.02), fatigue (p = 0.04), shortness of breath (p = 0.04), diarrhoea (p = 0.02) and a worse emotional functioning level (p = 0.03). Alcohol intake was independent of tumour stage (p = 0.48), employment status (p = 0.54), social class (p = 0.82), the time interval since laryngectomy (p = 0.64) and type of voice substitute (p = 0.76). The quality of life and mental state were independent of the amount of alcohol consumed. CONCLUSIONS: The results show that alcohol dependence is associated with adverse psychosocial and medical consequences, which require treatment. Socio-demographic and medical parameters do not allow any conclusions to alcoholism risk. Therefore, an individual exploration of the patients' drinking behaviour is needed, which could prepare the ground to specific treatment.

Hereditary spherocytosis and other hemolytic anomalies distort diabetic control by glycated hemoglobin.

Glycated hemoglobin (%HbA1c) has become a well established and reliable long term parameter indicative of the mean glucose load of the preceding 8 -10 weeks. A normal life span of approximately120 days of the red blood cells (RBC) is an essential condition. Hemolytic affections are characterized by a shorter life span, reducing the overall glucose uptake and %HbA1c. Measured %HbA1c is no longer correlated with mean blood glucose of the preceding period, simulating false low values. Underestimation of this kind is demonstrated for several hemolytic conditions, among them hereditary spherocytosis (HS). This latter, often harmless anomaly may lead to serious underestimation of glucose load. Recent investigations show not only a much higher incidence of HS than hitherto admitted (approximately 1 in 250 persons) but also an abnormally high incidence of diabetes in this hemolytic affection. In the presence of hemolysis %HbA1c is to be interpreted with caution. This justifies systematic detection of HS in routine hematology using--if available--the increase of the percentage of hyperchromic RBC.

Transfer of blood lymphocytes and macrophages between histocompatible progressor and regressor chickens infected with Rous sarcoma virus.

The development of histocompatible White Leghorn (progressor) and Arkansas Regression (regressor) chicken lines was described. When challenged with Rous sarcoma virus, progressor chickens developed fatal tumors while the regressor chickens eliminated the sarcoma. When sensitized histocompatible peritoneal macrophages and blood lymphocytes were transferred from regressor donors to progressor recipients, they both eradicated growing tumors. Histoincompatible cells were ineffective in inducing tumor remission. Within the two age groups tested, the sensitized blood lymphocytes and macrophages were only effective when transferred between age-matched donor and recipient chickens.

Multicenter evaluation of the Micral-Test II test strip, an immunologic rapid test for the detection of microalbuminuria.

OBJECTIVE: To assess the performance of the Micral-Test II immunologic test strip for the detection of microalbuminuria, a multicenter evaluation in eight European study sites was performed. RESEARCH DESIGN AND METHODS: Using both the Micral-Test II test strip and the routine method for the determination of albumin concentration, we investigated 2,228 urine samples from diabetic patients. Additionally, interperson variability, color stability, and possible interfering factors (temperature, pH, leucocyturia, erythrocyturia, and drugs) were tested. RESULTS: For a cutoff concentration of 20 mg/l with respect to the routine methods, a sensitivity of 96.7% and a specificity of 71% were calculated for the Micral-Test II test strip. The negative predictive value was 0.95, and the positive predictive value was 0.78, with a prevalence of positive samples (laboratory method) of 52%. The interperson variability of color interpretation showed 93% concordant readings. The interference study showed an influence of oxytetracycline, leading to higher readings. There was no interference from pH. A sample temperature of < 10 degrees C led to lower readings. In the case of samples with massive leucocyturia and erythrocyturia that may delete the chromatographic process, waiting an additional 1-2 min is needed before reading. CONCLUSIONS: The results of the multicenter evaluation show that the Micral-Test II test strip permits an immediate and reliable semiquantitative determination of low albumin concentrations in urine samples with an almost user-independent color interpretation.

Phenotypic and functional characteristics of circulating monocytes of elderly persons.

Aging is associated with impairment of immune functions. Age-dependent alterations in T-cells are well known. Although the pivotal role of monocytes in immune regulation by their production of proinflammatory and inhibitory cytokines is acknowledged, limited information is available on monocyte changes in aging. The present study focused on phenotypic changes in circulating monocytes in elderly subjects and in the level of cytokines they produce. The results demonstrated a significant expansion of CD14dim/CD16bright circulating monocytes in elderly. In contrast, the majority of circulating monocytes of healthy young individuals were CD14bright/CD16dim. The CD14dim/CD16bright monocytes are considered to have phenotypic evidence for activation. Furthermore, significant increases of constitutive production of monocytic cytokines including interleukin (IL)-1beta. IL-1 receptor antagonist, and IL-6 by nonstimulated monocytes from elderly was also indicative of activation. This was also observed when monocytes from elderly were cultured with autologous lymphocytes. However, after stimulation, significantly lowered IL-1beta production was observed and IL-6 and IL-10 tended to be higher in the elderly. Collectively, these results indicate that monocytes of aged individuals, in contrast to a younger population exhibit in vivo activation as well as imbalanced production of cytokines. Such age-related alterations in monocytes may contribute to impaired immune competence of aging.

Influence of urea on HbA1c-determinations by Menarini HA-8140 and on the difference between immunoturbidimetric and HPLC-HbA1c-results.

A secondary peak (#C) included in the HbA1c-calculation by the HA-8140 HPLC (Menarini) shows a fairly good correlation with serum urea. The correlation with HbA1c and with serum glucose is at first glance significant but reveals at a closer look being biased by some incorrect assumptions. The difference between immunoturbidimetric determination (Tinaquant HbA1c II Roche) and HPLC shows a similar behaviour to urea as does the #C-peak of the chromatographic separation. This peak as well as the difference between both determinations of HbA1c could be attributed to carbamylated haemoglobin. The definitive identity has to be proven. This peak could be a monitoring tool for long-time urea. The integration of this peak into total HbA1c by the HA-8140 (Menarini) can lead to a false diagnosis of diabetes in non-diabetic patients with elevated urea.

Models for depolymerizing enzymes: criteria for discrimination of models.

Several models for the action of alpha amylase have been proposed to account for the nonrandom distribution of oligosaccharides in the amylase digests of polysaccharides. The preferred-attack model attempts to account for the nonrandom distribution by assuming that the probability for bond cleavage depends upon the position of the bond in the chain. The repetitive, or multiple-attack, model suggests that the nonrandom distribution of oligosaccharides arises because an amylase can form a cage-like complex with a substrate and attack it several times during a single encounter. The multiple-enzyme or dual-site model suggests that the nonrandom yield of oligosaccharides arises from the combined action of exo- and endo-enzymes. The effects of pH, inhibitors, and substrate chain-length on enzyme action have been studied in several laboratories to determine which of the three action-patterns best describes the action of alpha amylase. The influence of these variables on product distributions or enzyme action-patterns are mathematically modeled in the Appendix. The experimental data on porcine-pancreatic alpha amylase are discussed in the light of the derivations.

Repetitive attack by Aspergillus oryzae alpha amylase.

The action of Aspergillus oryzae alpha amylase on reducing-end, and uniformly radiolabeled maltotriose through maltodecaose has been studied. The enzyme is found to hydrolyze more than a single glycosidic bond during enzyme-substrate encounters. The extent of this repetitive attack is quantitated.

Subsite mapping of enzymes: collecting and processing experimental data--a case study of an amylase-malto-oligosaccharide system.

Two research groups have independently developed the theory and experimental methodology for quantitatively assessing substrate monomer-subsite binding-energies for depolymerases. When the two approaches are applied to the same enzyme-substrate system they yield surprisingly divergent results. This paper outlines the application of the two approaches to an amylase-maltooligosaccharide system and points out the more important areas of disagreement. We show that by proper data-management, the conflicts between the tow laboratories are basically resolved. The complexities of the subsite model demand extensive data-gathering and exacting data-processing and verification that the computed model-parameters can faithfully reproduce the experimental data.

Stimulation of progressor and regressor chicken leukocytes with Con A, PHA-P, and Rous sarcoma tumor antigens.

Progressor (Pr) and regressor (R) chickens from the University of Arkansas lines were used as leukocyte donors. Peripheral blood leukocytes were stimulated with two mitogens, concanavalin A (Con A) and phytohemagglutinin-P (PHA-P). Both Pr and R leukocytes displayed the same Con A-stimulated dose dependency on blastogenesis. The regressor leukocytes were stimulated more than the progressor leukocytes at high concentrations of PHA-P. There did not appear to be any correlation between the response of individual chickens to mitogens and their ability to regress a Rous sarcoma. We concluded that the R-Rs-1 gene, which controls the animal's response to Rous sarcoma, and the Con A and PHA-P response genes are probably located at different loci in the chicken genome. Mitogen-induced blastogenesis does not appear to be a useful index to predict regression response in the chicken. Under our experimental conditions, regressor leukocytes showed a sensitization to sarcoma antigens, but the progressor leukocytes did not. The data suggest that the R-Rs-1 gene does not confer a generally enhanced immune status to the chicken but acts as an Ir response gene to augment the immune response to specific antigens.

Adaptation of the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay for the determination of virus-neutralizing antibodies using the virus-neutralization assay.

The tetrazolium salt MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] has been widely used for bioassays. Herein is described the use of the MTT dye with a virus-neutralization (VN) assay to titer infectious bursal disease virus (IBDV)-neutralizing antibodies. A standard VN assay using chicken embryo fibroblasts (CEFs) and IBDV was used for the assessment of IBDV-neutralizing antibodies. The percent of CEF killing due to IBDV was quantitated using MTT, and the absorbance (A) data were used to calculate the VN antibody titer. This method of calculation offers the expression of VN titer in terms of units of activity per unit of volume.

Efficacy of a novel infectious bursal disease virus immune complex vaccine in broiler chickens.

Two experiments were conducted to test the efficacy of a novel infectious bursal disease virus (IBDV) vaccine in broiler chickens with maternal IBDV immunity. The IBDV vaccine was formulated by mixing IBDV strain 2512 with bursal disease antibodies (BDA) to produce the IBDV-BDA complex vaccine. In Expt. I, 1-day-old Cobb x Cobb broiler chickens were vaccinated subcutaneously with either IBDV-BDA or commercial live intermediate IBDV vaccine (vaccine A) or were left unvaccinated. In Expt. 2, the vaccine A group was not included; instead, IBDV strain 2512 was included. Chickens were maintained in isolation houses. On day 28 (Expt. 1) and day 32 (Expt. 2) of age, chickens from each group were challenged with a standard USDA IBDV (STC strain) challenge. Challenged and unchallenged chickens were evaluated for their bursa/body weight ratios and antibody titers 3 days post-challenge. Bursae collected from Expt. 2 were examined histologically to evaluate bursal lesions and confirm gross examination. None of the unvaccinated chickens was protected against the challenge virus as evidenced by the presence of acute bursal lesions (edema/hemorrhage). All chickens receiving the IBDV-BDA complex or the IBDV strain 2512 (Expt. 2) were protected from the challenge virus as evidenced by no acute bursal lesions. Additionally, chickens receiving the IBDV-BDA complex vaccine or the IBDV strain 2512 had antibody titers to IBDV, indication the presence of an active immune response. In Expt. 1, chickens vaccinated with vaccine A and challenged had bursal lesions similar to those observed in the unvaccinated, challenged chickens. These chickens also showed no indication of active immunity against the virus. These results suggest that the 1-day-of-age-administered IBDV-BDA complex vaccine can induce active immunity and protection against a standard IBDV challenge in the face of variable levels of maternal IBDV immunity.

Determination of optimum formulation of a novel infectious bursal disease virus (IBDV) vaccine constructed by mixing bursal disease antibody with IBDV.

A novel vaccine against infectious bursal disease virus (IBDV) has been developed. The new vaccine was constructed by mixing bursal disease antibody (BDA) contained in whole antiserum with live IBDV before lyophilization. To establish various formulations of BDA and IBDV, several BDA doses between 5 units and 80 units of BDA/50 microliters were mixed with 100 EID50/50 microliters of IBDV suspension in Expt. 1; in Expt. 2, several IBDV doses between 10 EID50/50 microliters and 977 EID50/50 microliters of IBDV suspension were mixed with 24 units of BDA/50 microliters. Vaccine preparations were administered subcutaneously to the nape of 1-day-old specific-pathogen-free (SPF) chicks. Safety, potency, and immunogenicity of the different vaccine formulations were evaluated using bursal weight, bursal gross examination, and IBDV antibody titer. Some bursae were examined histologically to confirm gross examinations. Several vaccine formulations were safe and efficacious and met the safety, potency, and immunogenicity criteria. A vaccine construct of 100 EID50 mixed with 24 units of BDA was selected as the release dose. When administered at 1 day of age, the novel vaccine allows for delayed infection of the bursa until after days 6-8 of age in SPF chicks, while initiating potency and immunogenicity to an IBDV challenge. The addition of BDA to the IBDV results in a complex vaccine that allows for safer immunization in SPF birds than under administration of the vaccine virus without BDA.

Experimental investigations on the suitability of the carbon dioxide laser for stapedotomy.

Surgery of the footplate may cause a number of possible complications such as cochlear hearing defects or even complete loss of hearing. This has made it necessary to look for improved techniques. When a laser is used for stapedotomy, the energy transmitted to the cochlea must be reduced to the lowest possible level. We thus investigated the carbon dioxide laser to determine whether it would prove to be more advantageous than the argon laser. Animal experiments showed that CO2 laser irradiation is well tolerated. Tests performed on isolated petrous bone resulted in the development of a new surgical instrument suitable for stapedotomy using the CO2 laser. Temperature and pressure measurements were carried out on a simplified model of the human cochlea. Our findings indicated that, with both types of laser, the irradiation required to perforate the otosclerotically thickened footplate adversely affects temperature and pressure development in the cochlea.

Auditory brain stem response monitoring during middle ear surgery.

Conductive hearing loss can be determined in the course of middle ear surgery by sound probe stimulation and simultaneous recording of auditory brain stem responses. Mechanical properties of the ossicular chain, usually judged subjectively by the surgeon's visual and tactile senses, can be quantified objectively. Thus, disarticulation of ossicles can be localized precisely, and fixation of the head of the malleus can be differentiated from stapes fixation. Moreover, the function of the reconstructed ossicular chain or prosthesis may be ascertained.

Behavioral treatment of chronic psychogenic polydipsia with hyponatremia: a unique case of polydipsia in a primary care patient with intractable hiccups.

Psychogenic polydipsia is recognized as a dangerous and potentially life threatening disorder. Few studies have focused on the treatment of polydipsia presenting in the outpatient setting. A review of the behavioral treatment literature pertaining to psychogenic polydipsia is presented. This review is followed by a case illustration of an outpatient behavioral approach to the treatment of psychogenic polydipsia in a non-psychiatric, primary car, adult, male patient suffering from intractable hiccup. An ABA single-case design was used, with sodium concentration as the dependent variable. This behavioral method appears promising in settings where restriction of fluid intake is not practical.

Evaluation of the humoral immune response to different antigens in Arkansas Regressor and Progressor chickens.

Arkansas Regressor and Progressor chickens were re-evaluated for their immune response to different antigens. Chickens received i.v. injection of either SRBC (10 birds per line) or Salmonella pullorum (SP; 10 birds per line) at 7 wk of age, and sera were collected at 6, 13, and 20 d postimmunization. A third group of birds (10 birds per line) received and i.m. injection of GAT emulsion at 7 and 12 wk of age, and sera were collected at 10 and 14 wk of age. There were significant differences between the two lines in their humoral immunity to SRBC, SP, and GAT. Such results suggest genetic control of humoral immunity to these antigens in these lines. It is unknown whether humoral immunity to these antigens is correlated to regression of tumors induced by Rous sarcoma virus.