Activity tracker-based intervention to increase physical activity in patients with type 2 diabetes and healthy individuals: study protocol for a randomized controlled trial.

BACKGROUND: One relevant strategy to prevent the onset and progression of type 2 diabetes mellitus (T2DM) focuses on increasing physical activity. The use of activity trackers by patients could enable objective measurement of their regular physical activity in daily life and promote physical activity through the use of a tracker-based intervention. This trial aims to answer three research questions: (1) Is the use of activity trackers suitable for longitudinal assessment of physical activity in everyday life? (2) Does the use of a tracker-based intervention lead to sustainable improvements in the physical activity of healthy individuals and in people with T2DM? (3) Does the accompanying digital motivational intervention lead to sustainable improvements in physical activity for participants using the tracker-based device? METHODS: The planned study is a randomized controlled trial focused on 1642 participants with and without T2DM for 9 months with regard to their physical activity behavior. Subjects allocated to an intervention group will wear an activity tracker. Half of the subjects in the intervention group will also receive an additional digital motivational intervention. Subjects allocated to the control group will not receive any intervention. The primary outcome is the amount of moderate and vigorous physical activity in minutes and the number of steps per week measured continuously with the activity tracker and assessed by questionnaires at four time points. Secondary endpoints are medical parameters measured at the same four time points. The collected data will be analyzed using inferential statistics and explorative data-mining techniques. DISCUSSION: The trial uses an interdisciplinary approach with a team including sports psychologists, sports scientists, health scientists, health care professionals, physicians, and computer scientists. It also involves the processing and analysis of large amounts of data collected with activity trackers. These factors represent particular strengths as well as challenges in the study. TRIAL REGISTRATION: The trial is registered at the World Health Organization International Clinical Trials Registry Platform via the German Clinical Studies Trial Register (DRKS), DRKS00027064 . Registered on 11 November 2021.

A large proportion of people who inject drugs are susceptible to hepatitis B: Results from a bio-behavioural study in eight German cities.

BACKGROUND: People who inject drugs (PWID) are at high risk of hepatitis B virus (HBV) infection by sharing needles and drug use paraphernalia. In Germany, no routine surveillance of HBV prevalence and vaccination coverage among PWID exists. METHODS: Socio-demographic and behavioural data were collected between 2011 and 2014 through face-to-face interviews, during a bio-behavioural survey of PWID recruited in eight German cities. Dried blood spots (DBS) prepared with capillary blood were tested for HBV markers. Factors associated with past/current HBV infection and vaccination status were analysed by univariable and multivariable analysis using logistic regression. The validity of self-reported HBV infection and vaccination status was analysed by comparison to the laboratory results. RESULTS: Among 2077 participants, the prevalence of current HBV infection was 1.1%, of past HBV infection was 24%, and of vaccine-induced HBV antibodies was 32%. No detectable HBV antibodies were found in 43%. HBV infection status was significantly associated with study city, age, years of injecting, use of stimulants, migration status, and homelessness; HBV vaccination status was significantly associated with study city, age, and level of education. Correct infection status was reported by 71% and correct vaccination status by 45%. CONCLUSIONS: HBV seroprevalence among PWID was about five times higher than in the general population in Germany, confirming PWID as an important risk group. Targeted information campaigns on HBV and HBV prevention for PWID and professionals in contact with PWID need to be intensified. Routinely offered HBV vaccination during imprisonment and opioid substitution therapy would likely improve vaccination rates among PWID.

The use of a bacteria detection system to evaluate bacterial contamination in PLT concentrates.

BACKGROUND: Random-donor PLTs (RDPs) are functional at 7 days. Nevertheless, since the mid-1980s, concern for bacterial contamination has caused the storage period to be reduced to 5 days. The ability of a bacteria detection system (BDS, Pall) to determine bacterial contamination and permit extension of the PLT shelf life to 7 days was assessed. STUDY DESIGN AND METHODS: Blood was collected into CP2D and leukoreduced RDPs were prepared. Upon arrival at the hospital, a 2- to 3-mL aliquot was removed from each RDP and introduced into the Pall BDS pouch with a sterile docking device. The pouch was incubated at 37 degrees C for 24 hours and then the oxygen content was measured to determine bacterial contamination. Additionally, the RDPs were pooled and an aliquot was removed for culture with standard manual techniques. CCIs were calculated 1 hour after infusion. RESULTS: A total of 12,062 individual RDPs were tested. The Pall BDS detected bacteria in 5 units. All of these were positive on repeat sampling. Propionibacterium acnes, coagulase-negative Staphylococcus, and Bacillus species were confirmed by manual technique in 3 units, one could not be identified, and one was negative. Aliquots from PLT pools were positive in 80 of 2201 pools when tested by manual methods. Of these, 79 were false-positives and 1 unit contained coagulase-negative Staphylococcus. The Pall BDS was easy to use and required less than 5 minutes for all manipulations. After 7 days of storage, the PLTs gave an average CCI of 16 x 10(11)+/- 3.39 x 10(11) 1 hour after transfusion (n = 9). CONCLUSIONS: The Pall BDS permits evaluation of RDPs for bacterial contamination. Culture-negative PLTs were successfully transfused in our institution up to and including 7 days after storage with good CCIs.

Conditioned blood reperfusion during angioplasty (CoBRA) treatment of acute myocardial infarction.

Acute myocardial infarct (MI) results in ischemia distal to lesions which puts heart muscle at risk for reperfusion injury (RI). Neutrophils, platelets and complement are putative mediators of RI. Recent advances in filtration technology provide integrated neutrophil and platelet removal together with complement-attenuating properties in a single blood-conditioning device. The present study characterizes the properties of a blood-conditioning filter and describes its clinical effect when used in conjunction with active hemoperfusion for acute MI. The filter reduces leukocytes by 99.9998 +/- 0.0002% (p<0.0001) and platelets by 99.9934 +/- 0.0069% (p<0.0001). Human plasma, derived from heparinized blood that was 'conditioned' by filtration, was studied using the Langendorff isolated rabbit heart preparation. The deposition of membrane attack complex and the resultant functional myocardial impairments [reflected in hemodynamic and biochemical measurements, including developed pressure, coronary blood flow, lymph-derived myocardial creatine kinase (CK)] are significantly attenuated by blood conditioning. Integration of the blood-conditioning filter into an active hemoperfusion system during primary percutaneous transluminal coronary angioplasty (PTCA) for acute MI (n=8) did not delay the procedure or cause any complications. Reperfusion of occluded coronary arteries with 300 cm3 of conditioned blood led to significant improvement in echocardiographic global wall motion scores (in standard deviations) following treatment (-1.64 +/- 0.18 to -1.45 +/- 0.15, p=0.02). Initial reperfusion of totally occluded coronary arteries with conditioned blood leads to acutely improved ventricular function. Collectively, these data provide a strong indication for continued investigation of conditioned blood reperfusion in angioplasty following acute MI for the long-term effect upon recovery of salvagable myocardium.

Analysis of the risk of transmitting bovine spongiform encephalopathy through bone grafts derived from bovine bone.

Bone substitutes of bovine origin are widely used for treatment of bone defects in dental and orthopedic surgery. Due to the occurrence of BSE and the new variant of Creutzfeldt Jakob Disease risks of transmitting diseases through the use of such materials need to be carefully evaluated. Risk analysis can either be based on theoretical assessments or experimental evidence. Here we present a comparative study on two bovine bone substitutes (Bio-Oss and Osteograf/N) which is based on theoretical values. Furthermore, for one of these materials, i.e. Bio-Oss, the prion inactivation capacity of one of the production steps was experimentally evaluated. Theoretical and experimental data indicate that the use of these materials does not carry a risk of transmitting BSE to patients.

Sinus grafting with porous bone mineral (Bio-Oss) for implant placement: a 5-year study on 15 patients.

The efficacy of Bio-Oss as a graft material for sinus floor elevation was studied in 15 patients. A total of 20 sinus augmentation procedures was performed, and 6 months later 57 implants were placed into the augmented sinuses. New bone formation was confirmed in biopsies of 3 patients (new bone: 21.08% +/- 7.25% after 6 mo, 27.55% +/- 4.88% after 12 mo; Bio-Oss: 39.17% +/- 4.36% after 6 mo, 27.01% +/- 11.64% after 12 mo). After a mean loading period of 4.0 +/- 0.5 years (range 3.2 to 4.8 y), 56 implants remained in place. This study confirms Bio-Oss's good osteoconductive properties.

Process control procedures to augment quality control of leukocyte-reduced red cell blood products.

Quality control of leukocyte-reduced packed red cell units (LRprc) produced in blood facilities must conform to regulatory criteria, which state that units may not contain more than 1 x 10(6) to 5 x 10(6) white blood cells (WBC) per unit. The post-filtration WBC content of a total of n = 386 LRprc units was counted with a Nageotte chamber to model the probability that a unit would not meet the regulatory criteria. The distribution of the residual leukocyte counts is close to a negative binomial distribution (NBD) and is independent of the packed red cell volume filtered. The observed probability that a unit of blood has a residual WBC greater than 5 x 10(6) is 2.6 +/- 2.6 x 10(-3). A power analysis of the two-sample Kolmogorov-Smirnov (KS) test in this application shows that a sample size of 20 is sufficient for determining that the process is in control when an out of control process has a k NBD parameter greater than or equal to that of the in control process. The three out of control processes observed to date appear to have this property. A sample of size 80 may be necessary for confirming that process validation data sets conform to the larger 'reference' database (n = 386) for processes that are out of control in such a way that their k NBD parameter is less than the k parameter of the in control process.

White cell subsets in apheresis and filtered platelet concentrates.

BACKGROUND: White cell (WBC)-reduced platelet concentrates (PCs) are defined by their absolute WBC count, a criterion which provides no information regarding the various WBC subsets contained in the PC. These heterogeneous cells are known to mediate different physiologic and pathophysiologic functions and account for distinct adverse transfusion responses. This study describes a method which allows the detection and quantification of these subsets and characterizes their presence in a variety of platelet components. STUDY DESIGN AND METHODS: Random-donor pooled PCs (RD PCs) and single-donor apheresis PCs (SD PCs) were studied. RD PCs consisting of 6 units of 2- to 3-day old PCs were randomly assigned to be filtered with one of four WBC-reduction filters from three different manufacturers (n=34). The residual WBCs were pelleted by centrifugation and isolated on a density gradient. The various WBC subsets were quantified by flow cytometry in unfiltered and filtered PCs using fluorescence and two-angle light scatter. SD PCs obtained with two manufacturer's systems and three processing protocols (n=30) were studied in like manner. RESULTS: WBC counts for non-WBC-reduced PCs averaged 3 x 10(8) in RD PCs and ranged from 8.6 to 9.6 x 10(6) per SD PC. Residual WBC counts in filtered PCs ranged from 2.3 x 10(4) to 2.2 x 10(5) and those in WBC-reduced SD PCs averaged 2.2 x 10(5) per unit. The data demonstrate significant phenotypic differences among PCs produced with various procedures. All SD PCs and two of four filtered RD PCs contained five WBC populations including granulocytes and monocytes, while RD PCs filtered with the remaining manufacturer's devices contained only lymphocytes. CONCLUSION: The data confirm that distinct phenotypic differences exist among PCs prepared with different devices and/or procedures. It is suggested that as for non-generic pharmaceuticals, the clinical benefits of these various PCs should be individually proved.

Practical methods to improve transfusion safety by using novel blood unit and patient identification systems.

Human error is a leading cause of transfusion-associated death. Many of these events are associated with a failure to comply with established unit-recipient identification protocols. Although several dedicated systems designed to minimize this problem are currently available, none of them have been sufficiently challenged by the various conditions that exist in diverse clinical settings. However, data available for computer-based recognition procedures and for a disposable blood bag combination lock, which precludes access to the blood before it is properly identified, are encouraging.

Characterisation of a novel airway late phase model in the sensitized guinea pig which uses silica and Bordetella pertussis as adjuvant for sensitization.

The objective of the present investigation was to validate a novel model of allergic late phase reaction in the airways of conscious guinea pigs by monitoring airway function with CO2-forced respiration. In addition airway inflammation as one possible cause for the development of airway late phase reaction was characterized by a novel technique which consists of bronchoalveolar lavage via the orotracheal route. Guinea pigs were sensitized twice at 2-week intervals with ovalbumin in silica and Bordetella pertussis. Two weeks after the booster sensitization all guinea pigs showed an acute decrease of tidal volume under CO2-forced respiration 5-15 min after antigen challenge. In contrast 42 out of 68 (= 62%) screened guinea pigs exhibited airway late phase response between 4-10 h after aerosol antigen challenge. During a subsequent cross-over study methylprednisolone (twice at 16 and 1 h before ovalbumin) did not significantly interfere with the acute response. In contrast the airway late phase response as well the associated eosinophil influx into the bronchoalveolar lavage were attenuated by the steroid. In conclusion, the sensitization procedure in combination with the novel method for monitoring airway function allowed measurement of a reproducible airway late phase response in about 60% of sensitized guinea pigs. The sensitivity of exclusively the late phase response and eosinophil influx to treatment with a glucocorticoid not only correlates this model with clinical pharmacotherapy but also strengthens the inflammatory nature of this model.

Pharmacological characterisation of a new model of antigen-induced pulmonary late-phase reaction in the conscious guinea pig which uses additional polymyxin B inhalation.

The aim of the present study was to develop a new model of allergic late-phase reaction in the airways of conscious guinea pigs (GPs) and to characterise it by pharmacological intervention. GPs were pretreated with cyclophosphamide and sensitized with ovalbumin (OA) in Al(OH)3. Weekly inhalations of polymyxin B were performed before and during sensitization and continued throughout the study period. Under cover of 10 mg/kg i.p. mepyramine all GPs still exhibited a pronounced immediate reaction (IR), peaking during the first 15 min after OA. Nine out of 15 GPs demonstrated, during screening, a reproducible (twice) second phase (late phase reaction (LPR)] of decreased airflow and tidal volume (TV), peaking 4-8 h after OA. In a cross over study, methylprednisolone (MP) at 30 mg/kg p.o. (16 h and 1 h before OA) significantly inhibited the LPR at its peak (4-8 h) (peak decrease of TV to % of basal: control 49.4 +/- 3.7; MP 78.9 +/- 7.5; p < 0.01: n = 7). After another booster sensitization with 2 micrograms OA/GP under the same conditions, the Paf-antagonist WEB 2347 at 3 mg/kg p.o. (1 h before OA) inhibited the LPR at its peak again (peak decrease of TV to % of basal: control 57.3 +/- 3.5; WEB 2347 74.8 +/- 7.6: p < 0.01; n = 6). In conclusion more than 50% of repeatedly ovalbumin sensitized (and polymyxin B-treated) unanaesthetized GPs developed a reproducible pulmonary late phase reaction (LPR). The LPR peaked at 4-8 h after antigen-exposure. The inhibitory effect by a glucocorticoid and the Paf-antagonist WEB 2347 suggests the inflammatory nature of the LPR and the involvement of platelet-activating factor (Paf) in this model.

Multicenter evaluation of the 3% paraformaldehyde method for white cell counting in leukocyte-reduced red blood cells. BEST (Biomedical Excellence for Safer Transfusion) Working Party of the International Society of Blood Transfusion.

BACKGROUND/AIM: The 3% paraformaldehyde (PFA) method is a simple technique for counting residual white blood cells (WBC) in leukocyte-depleted red blood cells (RBC). Preliminary data suggested that its sensitivity is at least equal to PCR and flow cytometry. We report the results of a multicenter study conducted by the BEST Working Party to determine precision and accuracy of the 3% PFA method. STUDY DESIGN: In the 7 participating laboratories, 5 sets of samples containing nominal concentrations of 200, 100, 50, and 10 WBC/ml were prepared by diluting whole blood into 'WBC-free' RBC. Ten milliliters of each sample were processed using the 3% PFA method, which is based on erythrocyte lysis and WBC concentration into 5% of the original sample volume; a Nageotte chamber is used to count concentrated WBC. RESULTS: The precision of the technique varied according to the nominal concentration, ranging from a CV of 12% at 200 WBC/ml to 57% at 10 WBC/ml. The technique measured fewer than the nominal WBC concentrations (mean of all laboratories, -12.4%); underestimation was probably due to cell loss during sample manipulation. Overall accuracy was however acceptable, because statistical considerations establish that the actual WBC concentration would unlikely exceed 2 times the estimated count. CONCLUSIONS: The 3% PFA method is suitable for the enumeration of residual WBC at concentrations > or = 50/ml. It represents a useful tool for evaluation of high performance filters by reference laboratories.

Detection of undiagnosed coagulopathies using routine rapid heparin neutralization.

OBJECTIVE: To determine the most frequent clinical causes of a prolonged activated partial thromboplastin time (APTT) result, and to determine whether a new heparin-removal device (the Hepchek, Pall Biomedical, Glen Cove, NY 11542) is capable of efficiently detecting the causes of these values. DESIGN: A combination of chart review and laboratory testing comparing the criterion standard--the heparin chromogenic substrate assay--with the Hepchek. Laboratory investigations were blinded and controlled. SETTING: Inpatient, acute-care hospital. PATIENTS: A total of 1,000 hospital patients with a variety of hemostatic disorders. MAIN OUTCOME MEASURE: The extent to which the Hepchek accurately identified the etiology of a prolonged APTT result. RESULTS: The APTT was prolonged in 25.2% of samples. The presence of heparin in the sample was confirmed by chromogenic assay or by using the Hepchek heparin-removal filter. The presence of heparin was confirmed in 12.8% of all samples and in more than 50% of all abnormal samples. The cause of the abnormal APTT was often unappreciated by the clinician. Bayesian analysis of the Hepchek's ability to diagnose heparin correctly as the cause of the abnormal APTT showed a sensitivity of 100% and specificity of 99.9%. CONCLUSION: Use of the Hepchek in the routine clinical laboratory is an efficient and rapid method of detecting heparin as a cause of isolated prolonged APTT results, and should reduce demands for unwarranted coagulation analyses and inappropriate treatment with blood products.

Dissociation of airway responsiveness and bronchoalveolar lavage (BAL) cell composition in sensitized guinea-pigs after daily inhalation of ovalbumin.

The association between inflammatory cell influx, cell activation status and change of airway responsiveness to acetylcholine (ACh) after daily inhalation of ovalbumin (OA) in sensitized guinea-pigs was investigated. Starting 3 weeks after sensitization (OA at 50 mg/kg s.c.+i.p.) guinea-pigs were exposed daily to 2% OA (10 min; under cover of 0.5 mg/kg mepyramine i.p. 15 min before OA) for 2 weeks. Concentration-response curves (CRCs) for inhaled ACh were performed 24 h after the last OA-challenge and 24 h after another single OA-inhalation 1 week later. CRCs for inhaled ACh were neither affected 24 h after the last OA challenge (daily for two weeks) nor 24 h after another OA-inhalation one week later. In contrast, bronchoalveolar lavage (BAL) from repeatedly OA- sensitized/-challenged guinea-pigs immediately after the last CRC showed a significant increase of total cell count by about tenfold and increases in eosinophils by about 20-fold, neutrophils by 30-fold, macrophages by about fivefold and lymphocytes by about tenfold (P < 0.05, multiple Wilcoxon-test). In contrast, markers of cell activation (EPO, MPO) were significantly decreased (P < 0.05). Methylprednisolone almost completely prevented these changes in increased cell numbers and decreased cell activation (vs OA contr., P < 0.05). The lack of increased airway hyperresponsiveness despite a massive inflammatory cell influx suggests other factors controlling airway responsiveness than inflammation.

Massive blood transfusion: the blood bank perspective.

The pathophysiology and support of the massively transfused patient from the vantage of a blood banker is reviewed. Hypothermia, acidosis and shock must be reversed if blood component therapy is to be effective. Algorithms which employ ratios of various blood components have not proved themselves, nor are screening coagulation tests of value until they are remarkably abnormal. Thrombocytopenia, thrombocytopathy, and hypofibrinogenemia appear to be the parameters which predispose to continued bleeding and microvascular hemorrhage in these patients. A large part of the impaired hemostasis is due to a consumption coagulopathy rather than the anecdotal assumption that dilution of the hemostatic elements is to blame. Hypocalcemia, hypomagnesemia and hyperkalemia are rarely observed nor do they pose a problem for this group of individuals. The logistics of blood supply to the clinical areas are addressed by describing one system that has proved itself.

Paradoxic effect of multiple mild coagulation factor deficiencies on the prothrombin time and activated partial thromboplastin time.

Single coagulation factor deficiencies predictably prolong the prothrombin time (PT) and activated partial thromboplastin time (APTT) at levels below 35% of normal activity. Acquired coagulopathies generally are characterized by multiple coagulation factor deficiencies. The effect was studied of such combined deficiencies on the PT/APTT using plasma from patients congenitally deficient in specific factors and pooled normal plasma. The PT begins to lengthen when individual factor levels fall below 25%. The APTT becomes prolonged when the levels of Factor V fall below 45%; the levels of Factors II and XI fall below 40%; and the levels of Factors I, V, VII, VIII, IX, and XII fall below 25% of normal. When plasma samples containing 50% activity of a single factor and 100% of all other factors were prepared by mixing the congenitally deficient plasma samples with the normal pool, the resulting mixtures had normal PT and APTT values. However, when two of these 50% factor-deficient plasmas were combined so that the mixture contained 75% activity of two coagulation factors and 100% of all other factors, the resulting PT and APTT were prolonged over the clotting times of either 50% factor-deficient plasma. Similar findings were obtained in patients with mild factor reductions caused by warfarin treatment. These data indicate that prolongations of the PT and APTT in disorders of coagulation affecting multiple factors represent less of a reduction in factor levels than is generally appreciated. This may explain the poor clinical correlation between abnormalities in these test results and clinical bleeding in acquired disorders of hemostasis.

Effect of prestorage white cell reduction on bacterial growth in platelet concentrates.

Platelet concentrates stored with and without autologous white cells were produced from units of whole blood that had been purposefully contaminated with bacteria immediately after phlebotomy. The blood was inoculated with one of five species of bacterium at either 10 or 50 colony-forming units per mL. The growth of the organisms was quantified throughout the conventional 5-day, 22 degrees C storage period of the platelet concentrates. One species, Klebsiella pneumoniae, failed to grow in any of the components. The remaining species, Staphylococcus epidermidis, S. aureus, Enterococcus faecalis, and Salmonella enteritidis, achieved log growth after 1 day of storage and reached a relative maximum concentration by Day 3. Although the concentration of bacteria immediately after inoculation was lower in the units reduced in white cells by filtration, no significant differences were observed thereafter. Data from this in vitro study support the concept that prestorage white cell reduction of platelet concentrates should not increase the likelihood of transfusion-induced septicemia.

Prevention of growth of Yersinia enterocolitica in blood by polyester fiber filtration.

The ability of polyester white cell-reduction blood filters to prevent the growth of Yersinia enterocolitica in units of donated blood was studied. Sixteen units of freshly drawn blood were inoculated with 10, 50, 100, or 150 colony-forming units (CFU) per mL of a clinical isolate of Y. enterocolitica (serotype O:3). The units were subsequently fractionated into red cell concentrate and resuspended in AS-1 or AS-3 solution. One-half of the red cell concentrates in each solution were filtered within 15 hours of phlebotomy and stored for 42 days. The remaining units served as unfiltered controls. Bacterial growth was monitored by weekly cultures and, on the last storage day, by the presence of endotoxin and the formation of methemoglobin. One hundred twelve primary cultures (560 plates) were performed. Units collected in AS-1 and filtered remained sterile when initially inoculated with 50 CFU or less. Filtered units spiked with 100 CFU or less and collected in AS-3 remained sterile throughout their shelf life. All unfiltered units supported bacterial growth and the formation of endotoxin and methemoglobin. The filtration of freshly donated blood proves to limit the growth of Y. enterocolitica in red cell components.

Performance characteristics of state-of-the-art hematology analyzers.

Data were obtained from four state-of-the-art automated hematology analyzers and compared with those obtained from microscopic reference procedures. The instruments evaluated were the Technicon's H*1, Sysmex's NE-8000, Coulter's STKR, and Coulter's STKS. Accuracy was assessed by comparing machine-generated white blood cell and red blood cell profiles with those obtained manually by experienced laboratorians. Specimens used were actual clinical samples submitted for routine analysis. The precision of the instruments in counting and sizing blood cells was not significantly different at the clinical decision-making level and consistently exceeded that of the microscopic method. Significant shifts in the leukocyte population were detected with relatively similar sensitivity by all instruments. As expected, the oldest model's clinical efficiency was exceeded by that of the newer analyzers. None of the analyzers performed with an accuracy that permits the laboratory to completely eliminate a microscopic scan of a stained blood film obtained from a patient's initial specimen.