[First data from a digital health app for erectile dysfunction]. / Erste Daten aus einer digitalen Gesundheits-App für Erektionsstörungen.

PURPOSE: In a systematic data analysis, we evaluated the influence of a digital health app on erection scores as well as life quality and patient activation in a group of patients with erectile dysfunction. METHODS: In all, 44 participants took part in an evidence-based program for patients with erectile dysfunction. The in app 12-week program included pelvic floor exercises and physiotherapeutic and cardiovascular training. In addition, there where sessions on mindfulness and sexual therapy as well as useful information about erectile dysfunction and its causes, nutrition, and risk factors. The median age was 46 years (19-75 years). All patients answered IIEF­5, PAM-13 and QoL-Med questionnaires at the beginning and the end of the program. A total of 27 questionnaires could be evaluated at both times. RESULTS: The average improvement in IIEF­5 score was 4.5 points (p < 0.0001). 96% of patients showed overall improvement of erection scores. Improvement in life quality was shown in 93% of participants. Moreover, there was a significant increase in patient activation scores. CONCLUSION: We were able to show that a multimodal digital app for self-management of erectile dysfunction improved not only erection scores but also life quality and patient activation. We concluded that it is possible to reproduce results of analog studies in a digital setting. Digital solutions can help to include patients in their treatment and to put guideline suggestions into practice.

A computerized scoring system to improve assessment of heparin-induced thrombocytopenia risk.

Essentials Current risk scores for heparin-induced thrombocytopenia (HIT) are not computer-friendly. We compared a new computerized risk score with the 4Ts score in a large healthcare system. The computerized risk score agrees with the 4Ts score 85% of the time. The new score could potentially improve HIT diagnosis via incorporation into decision support. SUMMARY: Background (HIT) is an immune-mediated adverse drug event associated with life-threatening thrombotic complications. The 4Ts score is widely used to estimate the risk for HIT and guide diagnostic testing, but it is not easily amenable to computerized clinical decision support (CDS) implementation. Objectives Our main objective was to develop an HIT computerized risk (HIT-CR) scoring system that provides platelet count surveillance for timing and degree of thrombocytopenia to identify those for whom diagnostic testing should be considered. Our secondary objective was to evaluate clinical management and subsequent outcomes in those identified as being at risk for HIT. Methods We retrospectively analyzed data from a stratified sample of 150 inpatients treated with heparin to compare the performance of the HIT-CR scoring system with that of a clinically calculated 4Ts score. We took a 4Ts score of ≥ 4 as the gold standard to determine whether HIT diagnostic testing should be performed. Results The best cutoff point of the HIT-CR score was a score of 3, which yielded 85% raw agreement with the 4Ts score and a kappa of 0.69 (95% confidence interval 0.57-0.81). Ninety per cent of patients with 4Ts score of ≥ 4 failed to undergo conventionally recommended diagnostic testing; 38% of these experienced persistent, unexplained thrombocytopenia, and 4% suffered life-threatening thrombotic complications suggestive of undiagnosed HIT. Conclusion The HIT-CR scoring system is practical for computerized CDS, agrees well with the 4Ts score, and should be prospectively evaluated for its ability to identify patients who should be tested for HIT.

Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia.

Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT. SUMMARY: Background Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by antiplatelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have suboptimal operating characteristics. We previously developed a diagnostic algorithm for HIT that incorporated 'four Ts' (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% confidence interval [CI], 0.93-1.00). Objectives The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care. Methods A retrospective cohort comprised patients who had undergone anti-PF4/H ELISA and serotonin release assay (SRA) testing in our healthcare system from 2010 to 2014. We determined the algorithm recommendation for each patient, compared recommendations with the clinical care received, and enumerated consequences of discrepancies. Operating characteristics were calculated for algorithm recommendations using SRA as the reference standard. Results Analysis was performed on 181 patients, 10 of whom were ruled in for HIT. The algorithm accurately stratified 98% of patients (95% CI, 95-99%), ruling out HIT in 158, ruling in HIT in 10 and recommending an SRA in 13 patients. Algorithm adherence would have obviated 165 SRAs and prevented 30 courses of unnecessary antithrombotic therapy for HIT. Diagnostic sensitivity was 0.82 (95% CI, 0.48-0.98), specificity 0.99 (95% CI, 0.97-1.00), PPV 0.90 (95% CI, 0.56-0.99) and NPV 0.99 (95% CI, 0.96-1.00). Conclusions An algorithm incorporating 4Ts scoring and a stratified interpretation of the anti-PF4/H ELISA has good operating characteristics and the potential to improve management of suspected HIT patients.

[Quality and quality assurance of teaching in surgery - recommendations from a workshop of the surgical cooperative for quality assurance]. / Qualität und Qualitätssicherung der Lehre in der Chirurgie - Empfehlungen aus einem Workshop der Chirurgischen Arbeitsgemeinschaft für Qualitätssicherung.

The shortage of surgeons in the operative disciplines field has in recent years further increased. The training of a surgeon and the required lifestyle combined with the work-life balance of the surgeons are perceived as being less attractive, so that young doctors after finishing medical school rarely decide for surgical careers. Changes in the social environment outside of our clinics has resulted in a decline of the social prestige. The modified structural preconditions require a rethinking of the training processes for studying and working conditions in surgery. The quality of surgical education is therefore a cornerstone for the future development of our subject and is directly linked to the training and junior development. The CAQ meeting in Greifswald in February 2009, has focused on the teaching in surgery and developed together with medical students of different faculties solutions for the three major problem factors: teaching, training and junior development. The students are demanding clear guidelines regarding the required theoretical and practical knowledge in the form of catalogues or learning logs. The absence of intrinsic commitment to an excellent teaching and role model is due to the ongoing conflict between patient care and teaching. Because in teaching usually neither the quantity nor the quality will be systematically registered and no sanctions promote the lesson, so that the training is always considered as a last resort. One approach could be a scoring system for teaching that reflect the quantity and quality of teaching in points. The practical year needs to be reformed, since over 25% of the students spend their surgery part abroad, because they are afraid to be considered as cheap labour. Especially at this point, the lecturer is asked to reform the education of students during the practical year and to strengthen the role model for young academic teachers.

Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in advanced renal cell carcinoma: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

Apparent heparin resistance from elevated factor VIII during pregnancy.

BACKGROUND: Heparin resistance is the need for more than 35,000 units of heparin per 24 hours to achieve therapeutic activated partial thromboplastin time (APTT) values. Elevated factor VIII can cause apparent heparin resistance by suppressing the APTT result without inhibiting the antithrombotic effect of heparin. CASE: A 41-year-old gravida 2 para 0 presented at 25 weeks of a twin gestation with a deep venous thrombosis that required unusually high doses of heparin, resulting in hematuria. Apparent heparin resistance caused by elevated factor VIII was diagnosed, and the heparin dose was appropriately decreased with anti-Xa heparin monitoring. The deep venous thrombosis and hematuria resolved. CONCLUSION: Factor VIII rises significantly during pregnancy, and can cause apparent heparin resistance. When this occurs, anti-Xa heparin levels are superior to APTT for monitoring heparin therapy.

Effect of magnesium hydroxide on iron absorption following simulated mild iron overdose in human subjects.

OBJECTIVE: To determine the effect of oral magnesium hydroxide [Mg(OH)2] on iron absorption after simulated iron overdose in human subjects. METHODS: A randomized, controlled crossover study was conducted in healthy adult male human volunteers taking no medications. Subjects received an average of 5.0 mg/kg elemental iron orally followed 1 hour later by either oral administration of 4.5 g of Mg(OH)2 per g ingested elemental iron or no treatment. Serial serum specimens were obtained over the 12 hours following iron ingestion and stored at -60 degrees C until standard serum iron assay was performed. After a 2-week washout period, the subjects were enrolled in the alternative trial arm. Individual baseline diurnal variation in serum iron levels was determined over a 12-hour period on the day prior to each trial. Area under time-concentration curves (AUCs) were calculated, and the AUC due to experimental iron ingestion (deltaAUC) was determined by subtracting the baseline diurnal AUC from the experimental AUC for each subject. RESULTS: Thirteen healthy adult male subjects were enrolled. Mean +/- SEM for deltaAUC due to experimental iron ingestion followed by treatment with Mg(OH)2, 78 +/- 23 micromol(hr)/L, was significantly less than that followed by no treatment, 144 +/- 33 micromol(hr)/L (p = 0.03 by signed rank test). CONCLUSIONS: Magnesium hydroxide, administered 1 hour post-iron ingestion at an oral dose of 4.5 g per g elemental iron ingested, significantly reduced iron absorption during a 12-hour period following simulated mild iron overdose in healthy adult human volunteers.

Effect of high-dose oral ganciclovir on didanosine disposition in human immunodeficiency virus (HIV)-positive patients.

This study was designed to investigate the interaction between high-dose oral ganciclovir (6,000 mg/day) and didanosine at steady state in patients who were seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) infection. The study was conducted as an open-label, randomized, three-period crossover study. Patients received (in random order) multiple oral doses of didanosine 200 mg every 12 hours alone, ganciclovir 2,000 mg every 8 hours alone, and ganciclovir 2,000 mg every 8 hours in combination with didanosine 200 mg every 12 hours. Blood and urine samples for determinations of drug concentrations were obtained on day 3 of each dose regimen. When ganciclovir was administered either before or 2 hours after didanosine, the mean increases in maximum concentration (Cmax), area under the concentration-time curve (AUC0-12), and percent excreted in urine of didanosine were 58.6% and 87.3%, 87.3% and 124%, and 100% and 153%, respectively. There were no statistically significant effects of didanosine on the steady-state pharmacokinetics of ganciclovir in the presence of didanosine, irrespective of sequence of administration. There were no significant changes in renal clearance of didanosine, suggesting that the mechanism for the interaction does not involve competition for active renal tubular secretion. The mechanism responsible for increased didanosine concentrations and percent excreted in urine during concurrent ganciclovir therapy may be a result of increased bioavailability of didanosine. However, the mechanism appears to be saturated at oral ganciclovir doses of 3 g/day.

A computer alert system to prevent injury from adverse drug events: development and evaluation in a community teaching hospital.

CONTEXT: Adverse drug events (ADEs) are the most common type of iatrogenic injury occurring in hospitalized patients. Errors leading to ADEs are often due to restricted availability of information at the time of physician order writing. OBJECTIVES: To develop, implement, and evaluate a computer alert system designed to correct errors that might lead to ADEs and to detect ADEs before maximum injury occurs. DESIGN: Prospective case series. SETTING: A 650-bed community teaching hospital in Phoenix, Ariz. PATIENTS: Consecutive sample of 9306 nonobstetrical adult patients admitted during the last 6 months of 1997. INTERVENTIONS: Thirty-seven drug-specific ADEs were targeted. Our hospital information system was programmed to generate alerts in clinical situations with increased risk for ADE-related injury. A clinical system was developed to ensure physician notification of alerts. MAIN OUTCOME MEASURES: A true-positive alert was defined as one in which the physician wrote orders consistent with the alert recommendation after alert notification. RESULTS: During the 6-month study period, the alert system fired 1116 times and 596 were true-positive alerts (positive predictive value of 53%). The alerts identified opportunities to prevent patient injury secondary to ADEs at a rate of 64 per 1000 admissions. A total of 265 (44%) of the 596 true-positive alerts were unrecognized by the physician prior to alert notification. CONCLUSIONS: Clinicians can use hospital information systems to detect opportunities to prevent patient injury secondary to a broad range of ADEs.

Prevention of fetal and maternal cyanide toxicity from nitroprusside with coinfusion of sodium thiosulfate in gravid ewes.

Coadministration of sodium thiosulfate with sodium nitroprusside (SNP) to children and adults prevents increases in cyanide concentrations during anesthesia or long-term SNP infusions. We wondered whether maternally administered sodium thiosulfate would prevent increases in fetal red cell cyanide concentrations in gravid ewes receiving SNP infusions. Under anesthesia, the fetal head was delivered through a lateral hysterotomy for catheterization of the jugular vein; the fetus was left in utero. Six control ewes near term received SNP at 25 micrograms.kg-1.min-1 for 4 h. Norepinephrine was used to maintain maternal mean arterial pressure at 80% baseline values. Six experimental ewes received the same treatment except that sodium thiosulfate was infused with SNP (1 g sodium thiosulfate per 100 mg SNP). Serial red cell cyanide concentrations in ewes and fetuses were followed. One control fetal death resulted from abruptio placenta, and this ewe and fetus were excluded from analysis. An additional control ewe and fetus died from apparent cyanide poisoning late during the course of the experiment. While control ewes and fetuses suffered progressive increases in red cell cyanide concentrations into the toxic range, experimental ewes and fetuses never developed toxic red cell cyanide levels (ewes P < .003, fetuses P < .004). These data, if applicable to humans, suggest that coadministration of sodium thiosulfate with SNP to pregnant women at doses currently in use for nonpregnant patients will prevent fetal, as well as maternal, cyanide toxicity.

The effectiveness of implementing the weight-based heparin nomogram as a practice guideline.

OBJECTIVE: To determine the effectiveness of the nomogram in a community hospital that implemented it as a practice guideline. DESIGN: A nonexperimental, retrospective time series. SETTING: A 600-bed community teaching hospital and regional referral center in Phoenix, Ariz. PATIENTS: The study population included 591 consecutive patients with venous thromboembolism, treated over a 5-year study period. METHODS: During this period, the weight-based heparin nomogram was adapted into a preprinted order sheet and distributed to the hospital wards. The main outcome variables were the time to achieve a therapeutic activated partial thromboplastin time and the rate of bleeding complications. RESULTS: Voluntary implementation of the nomogram steadily increased, reaching 94%. Comparison of the periods before and after 50% implementation demonstrated an increase in initial heparin dose (1185 vs 1420 U/h, P < .001), a decrease in time to achieve therapeutic activated partial thromboplastin time (19.6 vs 11.8 hours), a decrease in the variance of this parameter (25 vs 4 hours, P < .001), and no change in bleeding rates. The proportion of patients achieving a therapeutic activated partial thromboplastin time within 24 hours decreased from 97% to 86% when the results from our previous randomized controlled trial (efficacy) are compared with the present results (effectiveness). CONCLUSIONS: The weight-based heparin nomogram was well accepted by clinicians at our institution and led to more aggressive heparin dosing and improvements in intermediate outcomes, without increasing bleeding. Mitigation of benefit is likely to occur when practice guidelines are moved from the realm of efficacy research into clinical practice. Therefore, the effectiveness of such measures requires monitoring.

New method to predict patients' intravenous heparin dose requirements.

OBJECTIVE: To predict intravenous heparin dose requirements of patients treated for thromboembolic disorders. DESIGN: A retrospective cohort study in which we used simple linear regression to predict patients' effective maintenance dose (EMD) of heparin (units/kg/hour needed to achieve and maintain APTT therapeutic range) from patients' "heparin responsiveness" (the APTT increase after the initial 6 hours of heparin treatment per units/kg/hour received). SETTING/PATIENTS: The model was derived from 46 patients treated at one hospital (Hospital A) and then tested in 42 patients treated at another hospital (Hospital B). MEASUREMENTS AND MAIN RESULTS: Among Hospital A patients, there was a strong linear correlation (r = -.880; p < .001) between EMD (mean 16.02 units/kg/hour; 95% CI 14.9, 17.15) and "heparin responsiveness" (HR): EMD = 25.651 - [95.118 x HR]. This model accurately predicted Hospital B patients' EMD: 97% (37/38) fell within the model's 95% prediction interval; the mean absolute difference between predicted and actual EMD was 1.73 units/kg/hour (95% CI 1.39, 2.08); and only 16% of patients had EMD's more than 3 units/kg/hour different from that predicted by the regression model. The model's accuracy was comparable to that of our gold standard, the weight-based heparin dosing nomogram. CONCLUSION: The infusion dose of intravenous heparin effective for an individual patient can be predicted accurately from the patient's body weight and APTT response to the initial 6 hours of treatment. Especially in hospitals where validated heparin dosing nomograms are not used, clinicians may find this simple technique useful in achieving timely therapeutic anticoagulation.

The effect of hypertonic sodium bicarbonate on QRS duration in rats poisoned with chloroquine.

OBJECTIVE: To determine efficacy of hypertonic sodium bicarbonate in narrowing QRS prolongation produced by chloroquine. DESIGN: Randomized, controlled animal experiment using an accepted rat model of sodium channel blockade. METHODS: Hypotension and widening of QRS complexes (lead II) of the ECG were produced in 16 rats by administration of a total of 87 mg/kg chloroquine intravenously over 20 minutes. Eight rats were treated with 6 mL/kg 1 M sodium bicarbonate intravenously over two minutes beginning ten minutes into the chloroquine infusion. Serial measurements of QRS duration and systolic blood pressure were obtained for 30 minutes. RESULTS: QRS intervals narrowed more rapidly in animals receiving sodium bicarbonate (p = .045), although the difference in mean rate of narrowing between groups was modest at only .23 msec/min. Because of large variances, no statistically significant differences could be demonstrated in systolic blood pressure. CONCLUSIONS: Hypertonic sodium bicarbonate partially reversed sodium channel blockade and resultant QRS interval prolongation produced by chloroquine in rats. These data should be interpreted with caution, given the need to extrapolate to humans and the modest effect of sodium bicarbonate on QRS narrowing.

[Aortitis and development of an aneurysm after PTA of distal aortic stenosis]. / Aortitis und Entstehung eines Aneurysmas nach PTA einer distalen Aortenstenose.

A 43-year-old woman was admitted with peripheral arterial occlusive disease (PAD), pelvis-type. The angiography showed a high-grade stenosis of the aortal bifurcation. A percutaneous transluminal angioplasty (PTA) in "kissing-balloon-technique" was performed. After 7 days the patient developed a sepsis with distinct back-pain. The ultrasound-B-scan and CT-scan of the abdomen showed the development of an infrarenal aortic aneurysm during a period of 29 days. Bacterial infection of the aorta was considered to be the reason of development of the aneurysm occurred. Immediate antibiotic therapy got the patient afebrile after 14 days. We implanted an aortobiiliacal Dacron graft 2 weeks later. The follow-up time was without complications except for two thrombotic occlusions of the graft after 4 and 19 months. Thrombectomy was carried out in both cases without complications.