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BACKGROUND: Areas of activity with many intersections pose an increased risk for errors and critical incidents. Therefore, procedures for acute pain therapy are potentially associated with an increased risk for adverse patient outcomes. OBJECTIVE: The aim was to identify and grade the risk of critical incidents in the context of acute pain management. MATERIAL AND METHODS: The register of the nationwide reporting system critical incident reporting system of the Professional Association of German Anesthesiologists, the German Society for Anesthesiology and Intensive Care Medicine and the Medical Center for Quality in Medicine (CIRSmedical Anesthesiology) was screened for incidents concerning pain management. Out of 5365 cases reported nationwide up to 24 March 2020, 508 reports with the selection criterion "pain" could be identified and reviewed and 281 reports (55%) were included in a systematic analysis. RESULTS: Of the 281 reports most came from anesthesiology departments (94%; 3% from surgery departments and 3% from other departments). The reported cases occurred most frequently on normal wards but a relevant proportion of the reports concerned intermediate and intensive care units or areas covered by a pain service (PS). Based on the description of the incident in the report, an involvement of the PS could be assumed for 42% of the cases. In terms of time, most of the events could be assigned to normal working hours (90%) and working days (84%; weekends 16%). The analyzed reports related to parenteral administration of analgesics (40%) and central (40%) or peripheral regional anesthesia procedures (23%) and 13% of the reports related to patient-controlled intravenous analgesia (PCIA; multiple answers possible). Most of the events were caused by technical errors, communication deficits and deviations from routine protocols. A relevant number of the cases were based on mix-ups in the administration route, the dosage, or the active agent. About one third of the sources of error were of an organizational nature, 59% of the cases posed a possible vital risk and in 16% of cases patients had vital complications. The risk grading by risk matrix resulted in an extremely high risk in 7%, a high risk in 62%, a moderate risk in 25% and a low risk in 6% of the cases. Comparing risk assessment of events with involvement of different analgesic methods, multiple medication, combination of analgesic methods or involvement of PS showed no significant differences. Likewise, no differences could be identified between the risk assessments of events at different superordinate cause levels. If more than one overriding cause of error had an impact, initially no higher risk profile was found. CONCLUSION: Incidents in the context of acute pain management can pose high risks for patients. Incidents or near-incidents are mostly related to mistakes and lack of skills of the staff, often due to time pressure and workload as well as to inadequate organization.

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BACKGROUND, OBJECTIVES: Deficits in the quality of pain management in hospitals have been described for years. The aim of this study was to assess structures and processes of pain management in departments for internal medicine in German hospitals. MATERIALS AND METHODS: Data were collected using a standardized telephone interview (non-university hospital departments) on a randomized sample of hospitals (circa 1/3 of hospitals); all German departments of university hospitals were invited to participate and questioned separately using an online questionnaire (SurveyMonkey®). RESULTS: Data from 139 non-university departments (response rate: 21%) and 33 university hospital departments (only 21 questionnaires were fully answered, response rate 17 and 11%, respectively) were collected. Of 619 non-university hospital departments contacted, 441 explicitly refused to participate in the survey, most often on the grounds that there was no interest in pain management. Pain was regularly recorded as an independent parameter during the medical visit in 89% of the non-university hospital and 96% of the university hospital departments; written standardized treatment protocols for pain therapy were available in 57% of the non-university hospital departments (54% university hospital departments). In 76% of the non-university hospitals departments (100% university hospital departments), an acute pain service was also available for patients of internal medicine departments for co-treatment. Written cooperation agreements were less common (35% non-university hospital departments, 18% university hospital departments). CONCLUSION: The described implementation of pain management was satisfying in the participating departments. However, in consideration of the low participation and high rejection of participation due to explicit disinterest in the topic, the results should be critically assessed and presumably characterized by a significant positive bias.

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BACKGROUND: Patient-controlled intravenous analgesia (PCIA) is a well-established technique in acute pain management and available in most German hospitals. Despite its widespread use, information on current clinical practice is limited. This investigation evaluated clinical practice and monitoring as well as PCIA-associated adverse events and critical incidents in German hospitals. METHODS: An invitation to participate in this online-survey was sent to 995 heads of anesthesiology departments belonging to the "German Society of Anaesthesiology and Intensive Care Medicine". RESULTS: Of the departments receiving the link, 244 took part (response rate 25%). PCIA was used in 193 of these hospitals (79%). All the following statements relate to the hospitals in which PCIA was used. Piritramide was the most frequently used opioid. In parallel with PCIA, additional nonopioid analgesics were used in 94% of the hospitals, and in 38%, additional slow-release oral opioids were used. Parenteral opioids were administered by the ward staff in 4% of the hospitals. In 75% of hospitals, there were standardized indications for PCIA therapy, with almost two thirds of respondents stating that PCIA was the technique of second choice if regional procedures were contraindicated or failed. In all, 76% of the hospitals had an acute pain service. Twenty-four percent of the hospitals regularly used PCIA in non-surgical patients. In pediatric patients, PCIA was used in 62 hospitals (32%). Only 31% of the hospitals reported the use of standardized protocols for the specific monitoring of patients' vital signs on general wards, exceeding general care. Of the department, 158 (82%) reported adverse events in connection with the use of PCIA within the six-month period preceding the survey (most frequently due to patients' noncompliance [52%], dislocated intravenous lines [41%], communication errors [16%], administration of additional analgesics [16%] and/ or sedatives [14%], problems with the pump [16%], programming errors [9%], incorrect opioid concentration in the reservoir [8%], non-observance of contraindications [7%], incorrect dosing [6%] and self-dosing by the patient [4%] or by third parties [3%], filling the reservoir with thewrong medication [2%]; and other problems [5%]). Only 35 of the hospitals (18%) reported no problems associated with PCIA therapy. Seventy-five of the 193 respondents (39%) stated that at least one critical incident had occurred in the context of the use of PCIA. This resulted in a total of 335 cases out of an estimate of 50.000 patients treated with PCIA. The respondents classified these as follows: I) 273 incidents requiring a prolonged stay in the recovery room, but without further complications, II) 58 requiring transfer to the intensive care unit, but without further complications, III) three resulting in permanent harm to the patient and IV) one resulting in the death of the patient. A comparison of the monitoring standards for PCIA showed that critical incidents were reported less frequently in hospitals with less intensive monitoring, and more frequently in hospitals with higher monitoring standards. CONCLUSION: PCIA is a frequently used analgesic technique in German hospitals. There were many differences in how PCIA therapy was applied and monitored on general wards. Adverse events occurred to a significant extent, with a considerable part of them, which might be preventable. Critical incidents were perceived more often when standards for monitoring on general wards were higher. Consented current recommendations regarding treatment and monitoring standards as well as the systematic recording of complications when using PCIA are pending.

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BACKGROUND: Standard protocols or algorithms are considered essential to ensure adequate analgesia. Germany has widely adopted postoperative protocols for pain management including oral opioids for rescue medication, but the effectiveness of such protocols has only been evaluated longitudinally in a before and after setting. The aim of this cohort analysis was to compare the effectiveness of an oral opioid rescue medication algorithm for postoperative management of pain to the gold standard of patient-controlled intravenous analgesia (PCIA). MATERIAL AND METHODS: This study compared cohorts of patients of two prospective observational studies undergoing elective total hip replacement. After surgery patients received piritramide to achieve a pain score of ≤3 on the numeric rating scale (NRS 0-10). A protocol was started consisting of oral long-acting oxycodone and ibuprofen (basic analgesia). Cohort 1 (C1, 126 patients) additionally received an oral opioid rescue medication (hydromorphone) when reporting pain >3 on the NRS. Cohort 2 (C2, 88 patients) was provided with an opioid by PCIA (piritramide) for opioid rescue medication. Primary endpoints were pain intensity at rest, during movement, and maximum pain intensity within the first 24 h postoperative. Secondary endpoints were opioid consumption, functional outcome and patient satisfaction with pain management. RESULTS: Pain during movement and maximum pain intensity were higher in C1 compared to C2: pain on movement median 1st-3rd quartile: 6 (3.75-8) vs. 5 (3-7), p = 0.023; maximum pain intensity: 7 (5-9) vs. 5 (3-8), p = 0.008. There were no differences in pain intensity at rest or between women and men in either group. The mean opioid consumption in all patients (combined PACU, baseline, and rescue medication; mean ± SD mg ME) was 126.6 ± 51.8 mg oral ME (median 120 (87.47-154.25) mg ME). Total opioid consumption was lower in C1 than C2 (117 ± 46 mg vs 140 ± 56 mg, p = 0.002) due to differences in rescue opioids (C1: 57 ± 37 mg ME, C2: 73 ± 43 mg ME, p = 0.006, Z = -2.730). Basic analgesia opioid use was comparable (C1: 54 ± 31 mg ME, C2: 60 ± 36 mg ME, p = 0.288, Z = -1.063). There were no differences in respect to the addition of non-opioids and reported quality of mobilization, sleep, frequency of nausea and vomiting, or general satisfaction with pain management. CONCLUSION: In this study PCIA provided a better reduction of pain intensity, when compared to a standardized protocol with oral opioid rescue medication. This effect was associated with increased opioid consumption. There were no differences in frequencies of opioid side effects. This study was a retrospective analysis of two cohorts of a major project. As with all retrospective studies, our analysis has several limitations to consider. Data can only represent the observation of clinical practice. It cannot reflect the quality of a statement of a randomized controlled trial. Observational studies do not permit conclusions on causal relationships.

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BACKGROUND: Opioids are often used for pain treatment, but the response is often insufficient and dependent on e.g. the pain condition, genetic factors and drug class. Thus, there is an urgent need to identify biomarkers to enable selection of the appropriate drug for the individual patient, a concept known as personalized medicine. Quantitative sensory testing (QST) and clinical parameters can provide some guidance for response, but better and more objective biomarkers are urgently warranted. Electroencephalography (EEG) may be suitable since it assesses the central nervous system where opioids mediate their effects. METHODS: Clinical parameters, QST and EEG (during rest and tonic pain) was recorded from patients the day prior to total hip replacement surgery. Postoperative pain treatment was performed using oxycodone and piritramide as patient-controlled analgesia. Patients were stratified into responders and non-responders based on pain ratings 24 h post-surgery. Parameters were analysed using conventional group-wise statistical methods. Furthermore, EEG was analysed by machine learning to predict individual response. RESULTS: Eighty-one patients were included, of which 51 responded to postoperative opioid treatment (30 non-responders). Conventional statistics showed that more severe pre-existing chronic pain was prevalent among non-responders to opioid treatment (p = 0.04). Preoperative EEG analysis was able to predict responders with an accuracy of 65% (p = 0.009), but only during tonic pain. CONCLUSIONS: Chronic pain grade before surgery is associated with the outcome of postoperative pain treatment. Furthermore, EEG shows potential as an objective biomarker and might be used to predict postoperative opioid analgesia. SIGNIFICANCE: The current clinical study demonstrates the viability of EEG as a biomarker and with results consistent with previous experimental results. The combined method of machine learning and electroencephalography offers promising results for future developments of personalized pain treatment.

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OBJECTIVE: Hypoglycemia is a serious complication of diabetes treatment. This retrospective observational study characterized hypoglycemia-related hospital emergency room (ER) and inpatient (in-pt) admissions and identified risk factors for 30-day all-cause and hypoglycemia-related readmission. RESEARCH DESIGN AND METHODS: 4476 hypoglycemia-related ER and in-pt encounters with discharge dates from 1/1/2009 to 3/31/2014 were identified in a large, multicenter electronic health record database. Outcomes were 30-day all-cause ER/hospital readmission and hypoglycemia-related readmission. Multivariable logistic regression methods identified risk factors for both outcomes. RESULTS: 1095 (24.5%) encounters had ER/hospital all-cause readmission within 30 days and 158 (14.4%) of these were hypoglycemia-related. Predictors of all-cause 30-day readmission included recent exposure to a hospital/nursing home (NH)/skilled nursing facility (SNF; OR 1.985, p<0.001); age 25-34 and 35-44 (OR 2.334 and 1.996, respectively, compared with age 65-74, both p<0.001); and African-American (AA) race versus all other race categories (OR 1.427, p=0.011). Other factors positively associated with readmission include chronic obstructive pulmonary disease, cerebrovascular disease, cardiac dysrhythmias, congestive heart disease, hypertension, and mood disorders. Predictors of readmissions attributable to hypoglycemia included recent exposure to a hospital/NH/SNF (OR 2.299, p<0.001), AA race (OR 1.722, p=0.002), age 35-44 (OR 3.484, compared with age 65-74, p<0.001), hypertension (OR 1.891, p=0.019), and delirium/dementia and other cognitive disorders (OR 1.794, p=0.038). Obesity was protective against 30-day hypoglycemia-related readmission (OR 0.505, p=0.017). CONCLUSIONS: Factors associated with 30-day all-cause and hypoglycemia-related readmission among patients with diabetic hypoglycemia include recent exposure to hospital/SNF/NH, adults <45 years, AAs, and several cardiovascular and respiratory-related comorbid conditions.

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We present the main features of the final prototype of a pulsed optical laser, developed for pump-probe and other experiments in conjunction with the femtosecond x-ray beams at the European X-ray free-electron laser facility. Adapted to the temporal x-ray emission pattern of the facility, the laser provides 10 Hz bursts of up to 600 µs duration with intra-burst pulse frequencies as high as 4.5 MHz. In this mode, we have generated pulses as short as 12 fs at 350 W average power during the burst and with beam qualities close to the diffraction limit. This is, to the best of our knowledge, the highest power to date of a few-cycle laser operating at a center wavelength of 800 nm. Important for experimental flexibility, the laser can be configured in various unique ways, enabling, e.g., energy scaling to >3 mJ per pulse through a frequency change down to 100 kHz and the generation of nearly transform limited pulses between 12 fs and 300 fs. In addition to the 800 nm femtosecond beam line, a synchronized long pulse (0.8 ps or 400 ps) 1030 nm beam can be utilized, offering up to 4 kW burst average power, i.e. up to 40 mJ per pulse at 100 kHz. Efficient nonlinear wavelength conversion and tuning through intrinsic and external means further enhance the capabilities of the laser.

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BACKGROUND: Standardized treatment approaches can improve the quality of the management of acute postoperative pain. AIM: The purpose of this study was to describe the content and structure of currently implemented standards for the management of acute postoperative pain in German hospitals and to better define the concept of a treatment standard for acute pain. MATERIAL AND METHODS: Written standardized treatment protocols from 68 hospitals for the management of acute postoperative pain were analyzed. The evaluation was based on the layout of processes, the baseline and rescue or on-demand analgesic medication and safety mechanisms. RESULTS: A treatment standard per hospital separated for adults (68 standards) and children (27 standards) was identified and analyzed. A baseline medication was provided in all standards for adults and in 89% for children. Of the 95 standards 68% routinely combined opioids and non-opioids as a basis (78% for adults and 42% for children). A way to adapt the baseline medication was described more often in standards for adults. Of the standards for adults 91% (85% for children) contained provisions for rescue or on-demand analgesia and half of them (both adults and children) included an immediate-release opioid formulation, which was readily available. For adults the availability was regulated by a predefined process in 29% of the standards (8% for children). In cases of persisting pain, repetition of the rescue medication was generally possible in 63% of adult standards (54% for children) but within 1 h after the first dose in only 43% (30% for children). Intervention limitations for application of the rescue medication (e.g., a defined score on the numeric rating scale) were set in 63% of adult standards (54% for children). A follow-up assessment of the pain intensity after a rescue medication was only required in approximately half of the standards and safety information or mechanisms were only rarely included. CONCLUSION: Content, structure and type of the evaluated treatment standards showed a considerable heterogeneity with respect to the availability of rescue and baseline medication. Safety aspects were not addressed in many cases. These findings show that despite the requirements of the German guidelines for treatment of perioperative and posttraumatic pain for treatment standards, there are still no practical recommendations with respect to contents and structure of such standards.

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BACKGROUND: The aim of this study was to analyze the degree of organization of different standard protocols for acute pain management, as well as the derivation and definition of typical but structurally different models. METHODS: A total of 85 hospitals provided their written standardized protocols for analysis. Protocols for defined target processes from 76 hospitals and another protocol used by more than one hospital were included into the analysis. The suggested courses of action were theoretically simulated to identify and characterize process types in a multistage evaluation process. RESULTS: The analysis included 148 standards. Four differentiated process types were defined ("standardized order", "analgesic ladder", "algorithm", "therapy path"), each with an increasing level of organization. These four types had the following distribution: 27 % (n = 40) "standardized order", 47 % (n = 70) "analgesic ladder", 22 % (n = 33) "algorithm", 4 % (n = 5) "therapy path". Models with a higher degree of organization included more control elements, such as action and intervention triggers or safety and supervisory elements, and were also associated with a formally better access to medication. For models with a lower degree of organization, immediate courses of action were more dependent on individual decisions. Although not quantifiable, this was particularly evident when simulating downstream courses of action. Interfaces between areas of hospital activity and a cross-departmental-boundary validity were only considered in a fraction of the protocols. Concepts from clinics with a certificate in (acute) pain management were more strongly process-oriented. For children, there were proportionately more simple concepts with a lower degree of organization and less controlling elements. CONCLUSION: This is the first analysis of a large sample of standardized protocols for acute pain management focusing on the degree of organization and the possible influence on courses of action. The analysis shows how different the structures and presumably the practical objectives of the various concepts are. The analyzed protocols with a lower degree of organization can manage only the assignment of a particular medication to the corresponding patient group, with a presumably high requirement for considerable implicit knowledge of the responsible employees. Accordingly, a requirement for such protocols should be that they not only describe the preferred standard therapy, but also define the interactions between the staff members involved. It remains questionable whether a protocol with a low level of organization and a comparably high requirement for implicit knowledge and individual action--also from nonmedical personnel--is able to ensure efficient pain therapy, particularly in view changing staff and dynamic responses to changing pain situations.

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We present an ultra-widely tunable non-collinear optical parametric oscillator with an average output power of more than 3 W and a repetition frequency of 34 MHz. The system is pumped by the second harmonic of a femtosecond Yb:KLu(WO4)2 thin-disk laser oscillator. The wavelength of the signal pulse can be rapidly tuned over a wide range from the visible to the NIR just by scanning the resonator length.

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BACKGROUND: Toll-like receptors (TLRs) are key players in innate immunity and are causally related to arterial occlusive disease and arterial remodelling. The release of proinflammatory cytokines following TLR ligand binding is increased in patients with unstable angina. OBJECTIVE: To examine the effect of a percutaneous coronary intervention (PCI) on TLR2 and TLR4 response and expression. METHODS: In 70 PCI patients, blood samples were gathered after sheath insertion and 2 hours after the catheterisation. TLR2 and TLR4 expression on, and tumour necrosis factor alpha (TNFalpha) levels in, monocytes were measured with flow cytometry. Whole blood was stimulated overnight with the TLR2 ligand Pam3Cys and the TLR4 ligand lipopolysaccharide. TNFalpha was determined in the stimulated samples and considered to be a measure of the TLR response. Baseline TLR expression and response were studied in relation to angiographic luminal stenosis and fractional flow reserve (FFR) measurement. RESULTS: A significant relation was found between TLR response and the angiographic percentage diameter stenosis, number of diseased vessels and FFR outcome. Furthermore, 2 hours after PCI a significant decrease in TLR2 and TLR4 response (p<0.001) and TLR2 and TLR4 expression (p = 0.001 and p = 0.068, respectively) was seen. CONCLUSION: TLR response is positively associated with percentage diameter stenosis, multivessel disease and FFR outcome. Systemic TLR2 and TLR4 response and expression decrease after PCI. These results suggests that the TLR signalling pathway encompasses a potential biomarker for myocardial ischaemia in stable coronary artery disease.

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OBJECTIVE: The aim of the study was to compare the incidence of anaemia in patients treated with zidovudine (ZDV) with that in patients treated with highly active antiretroviral therapy (HAART) not including ZDV. METHODS: Using HIV Insight, a database of abstracted US HIV care centre medical charts, ZDV-naïve patients starting ZDV-containing HAART were compared with those starting non-ZDV, nucleoside reverse transcriptase inhibitor-containing HAART. Cohorts were divided as follows: group 1: without baseline anaemia [haemoglobin (Hb) >or=11 g/dL]; group 2: with baseline anaemia (Hb <11 g/dL). The incidence of anaemia (anaemia diagnosis, Hb <11 g/dL, erythropoietic therapy or blood transfusion) was computed for group 1. The anaemia hazard ratio (HR) was adjusted using Cox regression. The rate of worsening anaemia (Hb decrease >or=1.0 g/dL) was computed for group 2. RESULTS: In group 1, the incidence of anaemia was 24.3 and 8.1 per 100 person-years in the ZDV and non-ZDV cohorts, respectively, after 6 months of follow-up, and 12.5 and 5.3 per 100 person-years after 24 months. Significant predictors of anaemia were ZDV, low initial Hb, injecting drug use, CD4 count <200 cells/microL and AIDS. The adjusted HR for ZDV was 1.6 (P=0.005). In group 2, the ZDV/non-ZDV risk ratio for worsening anaemia was 2.2 (95% confidence interval 1.1-4.3). CONCLUSIONS: Patients initiating ZDV-containing HAART are at greater risk of developing new anaemia or worsening anaemia than patients initiating non-ZDV-containing HAART.

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Managed care organizations are shifting from traditional utilization management programs to focus on initiatives that improve the health of an insured population. This strategy requires sophisticated data integration to identify at-risk individuals and track outcomes. Laboratory data are becoming increasingly valuable tools for managed care organizations and healthcare providers. The HEDIS Effectiveness of Care measures have incorporated laboratory data into several key performance indicators. By building a comprehensive repository of laboratory data that includes both procedure codes and laboratory values, managed care organizations can realize substantial savings by avoiding the costly medical record reviews required when administrative data are incomplete. In addition to tracking clinical outcomes, laboratory data provide the ability to risk-stratify a population to target high-risk individuals for case management and disease management interventions. Healthcare organizations face several challenges in the integration of laboratory data into medical databases and practice management software. Confidentiality is a key consideration in view of recent healthcare regulations. Providers of laboratory services should work collaboratively with organizations setting standards for healthcare informatics to facilitate the pooling of data for quality improvement and outcomes research. Health Level Seven, Inc. (HL7), Logical Observation Identifier Names and Codes (LOINC), and Systematized Nomenclature of Medicine (SNOMED) will likely play a key role in this process.

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