Value of a Panel of 6 Serum Biomarkers to Differentiate Between Healthy Controls and Mild Cognitive Impairment Due to Alzheimer Disease.

BACKGROUND: There is considerable evidence suggesting that inflammatory responses may be involved in the neurodegenerative cascade of Alzheimer disease (AD). Blood-based biomarker analysis of inflammatory markers indicative of dementia could serve as a minimally invasive and easy-to-administer diagnostic tool in primary care. MATERIAL AND METHODS: The authors quantified 6 markers (brain-derived neurotrophic factor, insulin-like growth factor 1, vascular endothelial growth factor, transforming growth factor-beta type 1, monocyte chemoattractant protein 1, and interleukin-18) in blood serum of 68 healthy blood donors (controls), 42 patients with AD at the dementia stage, 55 patients with AD at the stage of mild cognitive impairment (MCI-AD), and 25 patients with MCI non-AD. All patients have been fully characterized, including AD biomarker analyses in cerebrospinal fluid. Data were analyzed in an algorithm that was trained, validated, and then used for dichotomous classification of unknown data into data sets suspicious and not suspicious of AD. RESULTS: Using this algorithm, 47 of 55 MCI-AD (85.5%) and 20 of 25 MCI non-AD (80%) cases were classified as suspicious of AD. CONCLUSIONS: This panel of 6 markers in blood serum may indicate underlying neurodegenerative processes in patients with AD at the MCI stage. The authors assume that a deranged equilibrium of neuroprotective and inflammatory processes is an overall major cause for neurodegeneration and cognitive decline.

Current hepatitis E virus seroprevalence in Swiss blood donors and apparent decline from 1997 to 2016.

Background and aimHepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine. Studies from several European countries, including Switzerland, have reported high seroprevalence of hepatitis E as a consequence of endemic infections. Published HEV seroprevalence estimates within developed countries vary considerably; primarily due to improved diagnostic assays. The purpose of this study was to investigate the seroprevalence of anti-HEV IgG in Swiss blood donations. Methods: We used the highly sensitive Wantai HEV IgG EIA and assessed regional distribution patterns. We analysed age- and sex-matched archive plasma dating back 20 years from canton Bern to investigate recent changes in HEV seroprevalence levels. Results: On average, 20.4% (95% confidence intervals: 19.1-21.8) of the 3,609 blood samples collected in 2014-16 were anti-HEV IgG positive; however, distinct differences between geographical regions were observed (range: 12.8-33.6%). Seroprevalence increased with age with 30.7% of males and 34.3% of women being positive donors over > 60 years old. Differences between sexes may be attributed to dissimilarities in the average age of this group. Within the specified region of the Bern canton, overall prevalence has declined over two decades from 30.3% in 1997/98 to 27.0% in 2006 and 22.3% in 2015/6. Conclusions: HEV seroprevalence in Switzerland is high, but has declined over the last decades. The result shows that primarily endemic HEV infections occur and that current blood products may pose a risk to vulnerable transfusion recipients. Nucleic acid screening of all blood products for HEV will begin in November 2018.

Low-Frequency Blood Group Antigens in Switzerland.

BACKGROUND: High-frequency blood group antigens (HFA) are present in >90% of the human population, according to some reports even in >99% of individuals. Therefore, patients lacking HFA may become challenging for transfusion support because compatible blood is hardly found, and if the patient carries alloantibodies, the cross-match will be positive with virtual every red cell unit tested. METHODS: In this study, we applied high-throughput blood group SNP genotyping on >37,000 Swiss blood donors, intending to identify homozygous carriers of low-frequency blood group antigens (LFA). RESULTS: 326 such individuals were identified and made available to transfusion specialists for future support of patients in need of rare blood products. CONCLUSION: Thorough comparison of minor allele frequencies using population genetics revealed heterogeneity of allele distributions among Swiss blood donors which may be explained by the topographical and cultural peculiarities of Switzerland. Moreover, geographically localized donor subpopulations are described which contain above-average numbers of individuals carrying rare blood group genotypes.

PRO-ONKO-selection of patient-reported outcome assessments for the clinical use in cancer patients-a mixed-method multicenter cross-sectional exploratory study.

PURPOSE: Cancer patients frequently suffer from multiple symptoms often impairing functional status and health-related quality of life (HRQOL). A comprehensive assessment including patient-reported outcomes (PROs) is recommended to enable individualized supportive care. However, PRO assessments are still not part of routine clinical practice. Therefore, this project aimed to compile an item pool from validated assessment instruments to facilitate the use of PROs for clinical decision-making in oncology clinics. METHODS: This qualitative dominant mixed-method cross-sectional exploratory study was carried out in four centers and comprised two stages. Stage I: Six interdisciplinary focus groups were conducted to choose questionnaires meeting particular clinical requirements. Stage II: Adult patients with heterogeneous cancer diagnoses, receiving in- or out-patient treatment were asked to participate and complete the chosen questionnaires (participation 71/74). Resulting PROs were compared with clinical records. Health care professionals (HCPs) and patients rated the usefulness for routine clinical practice. RESULTS: The European Organisation of Research and Treatment of Cancer (EORTC) QLQ-C30 and Distress Thermometer were chosen for screening and M.D. Anderson Symptom Inventory (MDASI) and EORTC single items for monitoring. Comparison of n = 88 PRO assessments with clinical records showed consistent documentation of side effects like fever and emesis. Symptoms like fatigue, sadness, or sleep disturbance were not documented regularly in the medical records but captured by PRO assessments. Patients and HCPs judged the chosen questionnaires and electronic data collection as useful. CONCLUSIONS: Future studies should examine how PROs can complement or substitute routine documentation in order to achieve standardized assessment and documentation during the treatment process in different settings and examine possible benefits for patients.

Too Many Blood Donors - Response Bias in the Swiss Health Survey 2012.

BACKGROUND: Data on blood donor status obtained from general surveys and health interview surveys have been widely used. However, the integrity of data on self-reported blood donor status from surveys may be threatened by sampling and non-sampling error. Our study aimed to compare self-reported blood donors (including one-time as well as regular donors) from the Swiss Health Survey 2012 (SHS) with register-based blood donors recorded by blood establishments and evaluate the direction and magnitude of bias in the SHS. METHODS: We compared population-weighted SHS point estimates of the number of blood donors with their corresponding 95% confidence intervals to the respective figures from blood donor registries (birth cohorts 1978-1993) and estimates of donors based on period donor tables derived from blood donor registries (birth cohorts 1920-1993). RESULTS: In the birth cohorts 1978-1993, the SHS-predicted number of donors was 1.8 times higher than the respective number of donors based on registry data. Adjusting for foreign and naturalized Swiss nationals that immigrated after their 18th birthday, the SHS overall predicted number of donors was 1.6 times higher. Similarly, SHS estimates for the 1920-1993 birth cohorts were 2.4 and 2.1 times higher as compared to register-based estimates. Generally, the differences between SHS and register-based donors were more pronounced in men than in women. CONCLUSION: Self-reported blood donor status in the SHS is biased. Estimates of blood donors are substantially higher than respective estimates based on blood donor registries.

Epstein-Barr virus negativity among individuals older than 60 years is associated with HLA-C and HLA-Bw4 variants and tonsillectomy.

Epstein-Barr virus (EBV) infects ≈ 95% of the adult population. The factors that confer protection in the remaining ≈ 5% remain unknown. In an exploratory study, we assessed immunogenetic factors and tonsillectomy in a cohort of 17 EBV-negative and 39 EBV-positive healthy individuals aged >60 years. Analyses of HLA genotypes revealed an association between EBV negativity and the presence of HLA-C-35T/T and/or HLA-Bw4 alleles. In addition, EBV-negative donors presented with a history of tonsillectomy more often than EBV-positive donors.

Role of donor and recipient sex in platelet transfusion.

BACKGROUND: H-Y proteins are ubiquitously expressed Y chromosome-encoded minor histocompatibility antigens, which are relevant in the transplantation of hematopoietic stem cells (HSCT) and solid organs. No studies have so far analyzed whether H-Y incompatibility influences the outcome of platelet (PLT) transfusion. STUDY DESIGN AND METHODS: We studied the effect of donor and recipient sex on outcome of 9038 single-donor PLT transfusions. RESULTS: Using standard corrected count increment or percent PLT recovery (PPR) calculations, male patients showed inferior recovery rates, irrespective of donor sex. Using an adjusted PPR, which takes into account differences in blood volume between males and females, neither donor nor recipient sex played any role in PLT recovery after transfusion. Similarly, the time to next PLT transfusion was unaffected by both donor and recipient sex. In a subgroup analysis of patients with graft-versus-host disease after allogeneic HSCT, male recipients of a female allograft-which may carry anti-H-Y T cells and antibodies-had significantly lower time to next PLT transfusion. However, this occurred after both male donor and female donor PLT transfusions, arguing against an involvement of alloreactivity against H-Y antigens on PLTs. CONCLUSION: This large analysis found no evidence that donor-recipient sex matching influences the outcome of PLT transfusion.

Switching iron-deficient whole blood donors to plateletpheresis.

BACKGROUND: Iron deficiency is a frequent side effect of whole blood (WB) donation. In contrast, less red blood cell loss and therefore less iron loss results from plateletpheresis. STUDY DESIGN AND METHODS: WB donors presenting a decrease in either hemoglobin (Hb) or ferritin levels were offered to switch to plateletpheresis with or without iron supplementation. We analyzed the effect of this intervention on deferral rates for an insufficient Hb level in 168 donors. Further, we assessed how this intervention affected Hb and ferritin levels, anemia occurrence, and platelet (PLT) concentrate yields in the donors who presented at least four successive times for thrombapheresis. RESULTS: Switching WB donors to repetitive plateletpheresis procedures resulted in an increase of median Hb (+12 g/L, p < 0.001) and ferritin (+15.5 ng/mL, p = 0.002) values. Anemia and deferral rates were reduced by 23% (p = 0.004) and 13% (p < 0.001). Between high- and low-frequency apheresis donors, no significant differences in Hb and ferritin levels were found. Similarly, discrepancies in Hb and ferritin values between donors that adopted iron supplementation and those who did not were insignificant. The median PLT concentrate yield was 5.43 × 10(11) PLTs. CONCLUSION: Switching iron-deficient WB donors to plateletpheresis was an effective intervention that permitted us to correct low Hb and ferritin levels while retaining donors in our pool.

[Blood transfusions in the treatment of chronic anemia]. / Die Bluttransfusion in der Behandlung der chronischen Anämie.

Blood transfusion is a not causal therapeutic option in symptomatic anemia. For long time, since the discovery of the blood circulation and the first experiments in transfusion over 300 years ago, blood transfusions were the only possibility to improve the tissue oxygenation. Pretransfusion testing of the blood components as well as of the donor and the recipient has made transfusion of allogeneic blood increasingly safe. Despite transfusion reactions still do occur, they have considerably diminished, inter alia by the introduction of hemovigilance systems and decreasing the hemoglobin value used as transfusion trigger, hence performing less unnecessary transfusions. In chronic anemia, usually accepted transfusion triggers today are 70 g/l hemoglobin in patients without comorbidities. The use of erythropoetin stimulating agents is widely used and should - after a careful examination of the anemia - be considered early in the treatment plan in patients with chronic anemic.

Feasibility and acceptance of electronic quality of life assessment in general practice: an implementation study.

BACKGROUND: Patients' health related quality of life (HRQoL) has rarely been systematically monitored in general practice. Electronic tools and practice training might facilitate the routine application of HRQoL questionnaires. Thorough piloting of innovative procedures is strongly recommended before the conduction of large-scale studies. Therefore, we aimed to assess i) the feasibility and acceptance of HRQoL assessment using tablet computers in general practice, ii) the perceived practical utility of HRQoL results and iii) to identify possible barriers hindering wider application of this approach. METHODS: Two HRQoL questionnaires (St. George's Respiratory Questionnaire SGRQ and EORTC QLQ-C30) were electronically presented on portable tablet computers. Wireless network (WLAN) integration into practice computer systems of 14 German general practices with varying infrastructure allowed automatic data exchange and the generation of a printout or a PDF file. General practitioners (GPs) and practice assistants were trained in a 1-hour course, after which they could invite patients with chronic diseases to fill in the electronic questionnaire during their waiting time. We surveyed patients, practice assistants and GPs regarding their acceptance of this tool in semi-structured telephone interviews. The number of assessments, HRQoL results and interview responses were analysed using quantitative and qualitative methods. RESULTS: Over the course of 1 year, 523 patients filled in the electronic questionnaires (1-5 times; 664 total assessments). On average, results showed specific HRQoL impairments, e.g. with respect to fatigue, pain and sleep disturbances. The number of electronic assessments varied substantially between practices. A total of 280 patients, 27 practice assistants and 17 GPs participated in the telephone interviews. Almost all GPs (16/17 = 94%; 95% CI = 73-99%), most practice assistants (19/27 = 70%; 95% CI = 50-86%) and the majority of patients (240/280 = 86%; 95% CI = 82-91%) indicated that they would welcome the use of electronic HRQoL questionnaires in the future. GPs mentioned availability of local health services (e.g. supportive, physiotherapy) (mean: 9.4 +/- 1.0 SD; scale: 1 - 10), sufficient extra time (8.9 +/- 1.5) and easy interpretation of HRQoL results (8.6 +/- 1.6) as the most important prerequisites for their use. They believed HRQoL assessment facilitated both communication and follow up of patients' conditions. Practice assistants emphasised that this process demonstrated an extra commitment to patient centred care; patients viewed it as a tool, which contributed to the physicians' understanding of their personal condition and circumstances. CONCLUSION: This pilot study indicates that electronic HRQoL assessment is technically feasible in general practices. It can provide clinically significant information, which can either be used in the consultation for routine care, or for research purposes. While GPs, practice assistants and patients were generally positive about the electronic procedure, several barriers (e.g. practices' lack of time and routine in HRQoL assessment) need to be overcome to enable broader application of electronic questionnaires in every day medical practice.

Definition and quantification of six immune- and neuroregulatory serum proteins in healthy and demented elderly.

Aim: Blood-based biomarkers related to immune- and neuroregulatory processes may be indicative of dementia but lack standardization and proof-of-principle studies. Materials & methods: The blood serum collection protocol as well as the analytic procedure to quantify the markers BDNF, IGF-1, VEGF, TGF-ß 1, MCP-1 and IL-18 in blood serum were standardized and their concentrations were compared between groups of 81 Alzheimer's disease patients and 79 healthy controls. Results: Applying standardized methods, results for the quantification of the six markers in blood serum are stable and their concentrations significantly differ for all analytes except VEGF between patients diagnosed with Alzheimer's disease and healthy controls. Conclusion: Analyzing a panel of six markers in blood serum under standardized conditions may serve as a diagnostic tool in primary dementia care in the future.

Red blood cell use in Switzerland: trends and demographic challenges.

BACKGROUND: Several studies have raised concerns that future demand for blood products may not be met. The ageing of the general population and the fact that a large proportion of blood products is transfused to elderly patients has been identified as an important driver of blood shortages. The aim of this study was to collect, for the first time, nationally representative data regarding blood donors and transfusion recipients in order to predict the future evolution of blood donations and red blood cell (RBC) use in Switzerland between 2014 and 2035. MATERIALS AND METHODS: Blood donor and transfusion recipient data, subdivided by the subjects' age and gender were obtained from Regional Blood Services and nine large, acute-care hospitals in various regions of Switzerland. Generalised additive regression models and time-series models with exponential smoothing were employed to estimate trends of whole blood donations and RBC transfusions. RESULTS: The trend models employed suggested that RBC demand could equal supply by 2018 and could eventually cause an increasing shortfall of up to 77,000 RBC units by 2035. DISCUSSION: Our study highlights the need for continuous monitoring of trends of blood donations and blood transfusions in order to take proactive measures aimed at preventing blood shortages in Switzerland. Measures should be taken to improve donor retention in order to prevent a further erosion of the blood donor base.

Adverse events and retention of donors of double red cell units by apheresis.

BACKGROUND: Safety of double-erythrocyte (2RBC) collection and reasons for ceasing 2RBC donation were retrospectively analysed in the blood donor population of Basel, Switzerland. METHODS: Donors with at least 1 2RBC apheresis were included in the study. Minimal requirements were Hb ≥140 g/L and body weight ≥70 kg; serum ferritin (SF) values were measured routinely, but were not part of the selection criteria. 2RBC collections were performed with ALYX devices at 6-month intervals. Adverse events (AEs) were systematically recorded and classified according to the ISBT EHN 2008 criteria. Data of procedures were retrieved from the ALYX software. Demographics, apheresis data and AEs were analysed with descriptive statistics. RESULTS: Data of 4,377 2RBC aphereses performed in 793 donors (779 males) between 1(st) January 2003 and 31(st) May 2015 were evaluated. Mean donor age at first 2RBC donation was 44 years (standard deviation [SD] 21), median number of donations was 4 (interquartile range [IQR] 8); 32% of the donors underwent a single procedure. There were 161 AEs, mostly local haematomas (55%) and vasovagal reactions (20%); fatigue was reported in 6% of the cases and was more frequent than citrate toxicity. Two severe AEs were observed. The most frequent reasons for abandoning 2RBC donation were low SF levels and donor choice (both 11%), but most donors simply did not reply to invitations (16%). Overall, procedure-related causes (AEs, low SF levels, no time for apheresis, inadequate venous access) were observed in 14% of the cases. At the end of the observation period, 40% of the donors were still active blood donors, but only 20% were donating 2RBC. DISCUSSION: 2RBC donation is overall safe. Donor retention was low over a period of 11 years. An important reason for abandoning 2RBC was the detection of low SF levels. The impact of fatigue on donor retention and the course of iron stores after repeated 6-monthly 2RBC apheresis require further investigation.

Value of a standard urinary dipstick test for detecting microalbuminuria in patients with newly diagnosed hypertension.

PRINCIPLES: Microalbuminuria may indicate target organ damage in hypertensive patients. However, testing for microalbuminuria is not yet consistently used in general practice. This may be partly due to a lack of data regarding the diagnostic value of practice-based dipstick testing in newly diagnosed hypertension. Objectives were to assess the diagnostic value of a standard dipstick test for urinary protein excretion. METHOD: 186 patients who had been newly diagnosed with hypertension were screened for microalbuminuria. A spot urine sample from each of the subjects was evaluated by using a standard dipstick test (Combur 10, Roche Diagnostics GmbH, Mannheim, Germany) in a primary care setting. The albumin/creatinine ratio was used as the "gold standard". RESULTS: Dipstick testing for protein was positive in 31 urine samples (16.7% of the test samples). The albumin/creatinine ratio was elevated in 33 samples (17.7% of the test samples). The sensitivity of detecting microalbuminuria was 26%, specificity 89%, positive predictive value 45%, and the negative predictive was 88%. Repeated dipstick testing 48 hours after the initial testing in 40 randomly selected patients showed a good reproducibility (98%). CONCLUSIONS: In a primary care setting a positive standard dipstick test of a random spot urine in patients with newly diagnosed hypertension may indicate the presence of microalbuminuria with high specificity. However, because of its low sensitivity, the standard urinary dipstick test can not be recommended as the sole method of screening for renal target organ damage. In addition standard dipstick testing is important to exclude confounding factors that can falsify the measurement of urinary protein excretion.

[Documentation of electronic patient records (EPRS) in German general practices: a telephone survey]. / Elektronische Erfassung von medizinischen Daten in deutschen Hausarzt- praxen: Ein Telefon-Survey.

In Germany, use and contents of EPRs are largely unknown and expected to be highly variable, due to missing standards. We conducted a telephone survey to describe and compare computer documentation habits in general practices. Specifically, we were interested in: (1) the type of medical data recorded; and (2) which factors influence the extent to which doctors used the EPR while seeing their patients. The sampling frame consisted of family physicians participating in a general practice research project: 32% (145/452) of family physicians in the district of Göttingen, Lower Saxony, and 63% (52/83) of physicians from a quality assurance network of family practices in the district of Freiburg, Baden-Württemberg. With the exception of two practices in Göttingen, all practices (n = 165 of 167) took part in this survey. Diagnoses, digital codes for service fees, and prescriptions were computerized in nearly all practices, although doctors were significantly more involved in Freiburg than in Göttingen. Clinical symptoms and findings were recorded in 80% of Freiburg and 52% of Göttingen practices (p = 0.008). Overall, in 74% of Freiburg and 51% of Göttingen practices, the physicians opened the EPR while seeing patients (p = 0.022). Nearly half of the Göttingen practices (49%) and 24% of the Freiburg practices (p < 0.05) entered digital codes for service fees and diagnoses on paper before entering them electronically. In multivariate models adjusting for sex, target group and training specialty, internet access in the office was independently predictive of 'EPR-activity' (OR: 2.23; 95%-confidence interval: 1.12-4.43). There seems to be room for improvement in terms of degree and intensity of recording of clinically-relevant data. Technical interest, i.e., internet access in the office, seems to enhance electronic documentation activities.

Acute renal failure on immune reconstitution in an HIV-positive patient with miliary tuberculosis.

Immune reconstitution syndrome following HAART in human immunodeficiency virus (HIV)-infected patients is characterized by inflammatory worsening of organ functions despite improvement in HIV surrogate markers of HIV infection. We describe a patient with miliary tuberculosis and urinary shedding of acid fast bacilli who developed acute renal failure 8 weeks after initiation of antituberculosis therapy and 6 weeks after initiation of HAART. The diagnostic workup and further course of disease implicated immune reconstitution syndrome as the cause of acute renal failure.

A new instrument to describe indicators of well-being in old-old patients with severe dementia--the Vienna List.

BACKGROUND: In patients with very severe dementia self-rating of quality of life usually is not possible and appropriate instruments for proxy-ratings are not available. The aim of this project is to develop an instrument of clinical proxy-ratings for this population. METHODS: Using electronic instruments, physicians and nurses recorded patient behaviour and changes of behaviour over a period of one year. Based on these data a list of 65 items was generated and subsequently allocated to 14 categories. This list was tested in 217 patients (61-105 yrs) with dementia diagnosed according to ICD-10 by both physicians and nurses. The severity of dementia was assessed by means of the Global Deterioration Scale (GDS) and the Brief Cognitive Rating Scale (BCRS). The Spitzer-Index (proxy-rating) was used as a global quality of life measure. Activity of daily living was rated using the Barthel Index. RESULTS: A factor analysis of the original 65 items revealed 5 factors (communication, negative affect, bodily contact, aggression, and mobility). By stepwise removing items we obtained satisfactory internal consistencies of the factors both for nurses' and physicians' ratings. The factors were generally unrelated. The validity of the instrument was proven by correlations of the factors communication and mobility with the Brief Cognitive Rating Scale (BCRS) and the Barthel-Index. CONCLUSION: The results demonstrate the reliability and validity of the Vienna List as a proxy rating measurement of quality of life in patients with severe dementia. The psychometric properties of the scale have to be proved in further studies.

Platelet transfusion: basic aspects.

Platelet transfusions have been shown to prevent major haemorrhage and improve survival in thrombocytopenic patients. Since then, advances in the preparation of platelet components, including the introduction of pathogen reduction techniques, have been achieved. The number of transfused platelet components is still growing owing to the increasing number of patients treated for haemato-oncological diseases. Additionally, indications have been extended, for example to patients with drug-induced platelet dysfunction. This review focuses on current platelet component production and storage techniques, including pathogen reduction, indications for platelet transfusion and safety issues including alloimmunisation and management of platelet refractoriness.