[Frequency and barriers to the patient advanced directive and lasting power of attorney: findings from a prospective observation study in palliative care services]. / Häufigkeit und Barrieren bei Patientenverfügung und Vorsorgevollmacht: Erkenntnisse aus einer prospektiven Observationsstudie im palliativmedizinischen Dienst.

BACKGROUND: The advance directive and lasting power of attorney are instruments to strengthen patients' autonomy. A hospital-based palliative care consultation service can advise patients and family members about these instruments. This study investigates the need for such consultation among patients with life-limiting illness. METHODS: This prospective observational study on intensive and non-intensive care units includes patients with a request for palliative care consultation. Patient-related factors were evaluated for their possible association with the presence or absence of advance directives or power of attorney. In addition, focus group interviews with members of the palliative care consultation team were carried out to identify barriers which prevent patients from drawing up such documents. RESULTS: A total of 241 oncological and 53 non-oncological patients were included with a median age of 67 years; 69 (23%) patients were treated in the intensive care unit (ICU). Overall, 98 (33%) patients had advance directives, and 133 (45%) had determined a legal health care proxy in advance. A total of 52 patients died in hospital (17.7%). Only age and relationship status were associated with directives. In interviews, the following barriers were identified: information deficit, concern regarding discontinuation of treatment, loss of autonomy and wish to avoid a burden for the family. CONCLUSION: The majority in this severely ill patient population lack advance directives. In order to remove barriers, more effective information and counseling is required about such directives. In particular, guidance should include potential clinical situations in which such directives are potentially beneficial.

Translation of Experimental Findings from Animal to Human Biology: Identification of Neuronal Mineralocorticoid and Glucocorticoid Receptors in a Sectioned Main Nerve Trunk of the Leg.

The activation of the mineralocorticoid (MR) and glucocorticoid (GR) receptors on peripheral sensory neurons seems to modify pain perception through both direct non-genomic and indirect genomic pathways. These distinct subpopulations of sensory neurons are not known for peripheral human nerves. Therefore, we examined MR and GR on subpopulations of sensory neurons in sectioned human and rat peripheral nerves. Real-time PCR (RT-PCR) and double immunofluorescence confocal analysis of MR and GR with the neuronal markers PGP9.5, neurofilament 200 (NF200), and the potential pain signaling molecules CGRP, Nav1.8, and TRPV1 were performed in human and rat nerve tissue. We evaluated mechanical hyperalgesia after intrathecal administration of GR and MR agonists. We isolated MR- and GR-specific mRNA from human peripheral nerves using RT-PCR. Our double immunofluorescence analysis showed that the majority of GR colocalized with NF200 positive, myelinated, mechanoreceptive A-fibers and, to a lesser extent, with peripheral peptidergic CGRP-immunoreactive sensory nerve fibers in humans and rats. However, the majority of MR colocalized with CGRP in rat as well as human nerve tissue. Importantly, there was an abundant colocalization of MR with the pain signaling molecules TRPV1, CGRP, and Nav1.8 in human as well as rat nerve tissue. The intrathecal application of the GR agonist reduced, and intrathecal administration of an MR agonist increased, mechanical hyperalgesia in rats. Altogether, these findings support a translational approach in mammals that aims to explain the modulation of sensory information through MR and GR activation. Our findings show a significant overlap between humans and rats in MR and GR expression in peripheral sensory neurons.

Influence of Cannabinoid Treatment on Trajectories of Patient-Related Outcomes in Chronic Pain: Pain Intensity, Emotional Distress, Tolerability and Physical Disability.

The treatment of chronic pain with cannabinoids is becoming more widespread and popular among patients. However, studies show that only a few patients experience any benefit from this treatment. It also remains unclear which domains are affected by cannabinoid treatment. Therefore, the present study is novel in that it explores the effects of cannabinoid treatment on four patient-related outcome measures (PROMs), and includes patients with chronic refractory pain conditions who have been given the option of cannabinoid treatment. A retrospective design was used to evaluate the impact of cannabinoid treatment on patients with refractory pain in two German outpatient pain clinics. The present study shows that pain intensity (mean relative reduction (-14.9 ± 22.6%), emotional distress (-9.2 ± 43.5%), pain-associated disability (-7.0 ± 46.5%) and tolerability of pain (-11 ± 23.4%)) improved with cannabinoid treatment. Interestingly, the trajectories of the PROMs seemed to differ between patients, with only 30% of patients responding with respect to pain intensity, but showing improvements in other PROMs. Although the mean treatment effects remained limited, the cumulative magnitude of change in all dimensions may affect patients' quality of life. In summary, a singular evaluation with pain intensity as the sole outcome does not cover the multidimensional effects of cannabinoids. Therefore, the treatment effects of cannabinoids should be evaluated with different PROMs.

Supplementing transcranial direct current stimulation to local infiltration series for refractory neuropathic craniocephalic pain: A randomized controlled pilot trial.

Background: Some patients with neuralgia of cranial nerves with otherwise therapy-refractory pain respond to invasive therapy with local anesthetics. Unfortunately, pain regularly relapses despite multimodal pain management. Transcranial direct current stimulation (tDCS) may prolong pain response due to neuro-modulatory effects. Methods: This controlled clinical pilot trial randomized patients to receive anodal, cathodal or sham-tDCS stimulation prior to local anesthetic infiltration. Pain attenuation, quality-of-life and side effects were assessed and compared with historic controls to estimate effects of tDCS stimulation setting. Results: Altogether, 17 patients were randomized into three groups with different stimulation protocols. Relative reduction of pain intensity in per protocol treated patients were median 73%, 50% and 69% in anodal, cathodal and sham group, respectively (p = 0.726). Compared with a historic control group, a lower rate of responders with 50% reduction of pain intensity indicates probable placebo effects (OR 3.41 stimulation vs. non-stimulation setting, NNT 3.63). 76.9% (n = 10) of tDCS patients reported mild side-effects. Of all initially included 17 patients, 23.5% (n = 4) withdrew their study participation with highest proportion in the cathodal group (n = 3). A sample size calculation for a confirmatory trial revealed 120 patients using conservative estimations. Discussion: This pilot trial does not support series of anodal tDCS as neuro-modulatory treatment to enhance pain alleviation of local anesthetic infiltration series. Notably, results may indicate placebo effects of tDCS settings. Feasibility of studies in this population was limited due to relevant drop-out rates. Anodal tDCS warrants further confirmation as neuro-modulatory pain treatment option.

Factors Influencing Antibody Response to SARS-CoV-2 Vaccination.

Vaccination plays a key role in tackling the ongoing SARS-CoV-2 pandemic but data regarding the individual's protective antibody level are still pending. Our aim is to identify factors that influence antibody response following vaccination in healthcare workers. This single-center study was conducted at Evangelische Kliniken Gelsenkirchen, Germany. Healthcare workers were invited to answer a questionnaire about their vaccinations and adverse reactions. Subsequently, the level of anti-receptor binding domain (RBD) IgG antibody against SARS-CoV-2's spike protein through blood samples was measured. For statistics, we used a defined correlation of protection (CoP) and examined risk factors associated with being below the given CoP. A total of 645 employees were included and most were female (n = 481, 77.2%). A total of 94.2% participants had received two doses of vaccines (n = 587) and 12.4% (n = 720) had been infected at least once. Most common prime-boost regimen was BNT162b2 + BNT162b2 (57.9%, n = 361). Age (p < 0.001), days since vaccination (p = 0.007), and the homologous vaccination regimen with ChAdOx + ChAdOx (p = 0.004) were risk factors for the antibody level being below the CoP, whereas any previous COVID-19 infection (p < 0.001), the number of vaccines (p = 0.016), and physical complaints after vaccination (p = 0.01) were associated with an antibody level above the CoP. Thus, age, vaccination regimen, days since vaccination, and previous infection influence the antibody level. These risk factors should be considered for booster and vaccinations guidelines.

[Support of opioid rotation using online apps : Evaluation of applicability and comparison to the LONTS guidelines]. / Unterstützung der Opioidrotation mithilfe von Online-Apps : Evaluation der Anwendbarkeit und Vergleich mit der LONTS-Leitlinie.

BACKGROUND: Opioid rotation can be indicated due to drug side effects, drug interactions or inadequate effect of treatment with opioids. For the determination of the oral morphine equivalence, a practice tool has been published with the long-term use of opioids in chronic nontumor-related pain (LONTS) guidelines. In contrast, several apps are available that have not yet been evaluated. MATERIAL AND METHODS: Apps and web applications for opioid conversion were searched using Google Play Store®, iOS App Store® and the Google® search engine. German and English language apps with calculator functions were included. Using the apps, 16 test cases from clinical practice were calculated and the deviation from the recommendation of the LONTS guidelines was calculated. RESULTS: A total of 17 apps were identified, 11 named the origin of the algorithm and 3 of them defined the literature sources. None of the apps and web applications had a quality seal, and none could solve all cases. Deviations of the resulting oral morphine equivalents of up to 179% from the guideline-compliant conversion were identified and 4 apps warned for overdosing. CONCLUSION: Although the apps and web applications simplify conversion between opioids, there is high variance in conversion factors and sometimes a relevant deviation from evidence-based tables. Overall, there is a high risk of false opioid dosing.

Behaviour-based pain scales: Validity and interrater reliability of BPS-NI and PAINAD-G on general wards.

BACKGROUND: Measuring pain intensity in patients unable to communicate is a challenge on general wards. Observation-based pain scoring tools have been used for patients with dementia or in critically ill intensive care unit (ICU) patients. However, there is no established or validated assessment tool for non-ICU patients without dementia related cognitive deficiencies who cannot communicate. The "Behavioural Pain Scale Non-Intubated" (BPS-NI) and the "Pain Assessment In Advanced Dementia-German" (PAINAD-G) are potential tools to fill this gap. METHODS: This study was performed with verbal non-ICU patients on general wards at Charité Berlin. Two assessors independently rated pain intensity using the BPS-NI and the PAINAD-G along with patients' self-ratings on the Numeric Rating Scale (NRS). The interrater-reliability of BPS-NI and PAINAD-G was calculated and ROC-analyses were performed to identify cut-off values for medium and intense pain for each score. Effectiveness was calculated using percentage agreement. In total, 126 patients were included into analysis. RESULTS: The BPS-NI showed substantial congruence in interrater-reliability (Cohens-Kappa 0.71), whereas the PAINAD-G showed moderate congruence (Kappa 0.48). Based on ROC-analyses, for medium pain levels a cut-off 4 (BPS-NI) or 2 (PAINAD-G) and for severe pain levels cut-off 5 (BPS-NI) and 3 (PAINAD-G) would result in good accordance with self-reported NRS for pain. CONCLUSION: The BPS-NI shows a good validity in measuring pain intensity in patients on general wards and may possibly be used for patients unable to communicate. Using defined cut-off values for BPS-NI and PAINAD-G, clinically relevant pain intensities in patients can reliably be detected. SIGNIFICANCE: Measuring the pain intensity in patients unable to communicate is a common challenge on general wards. This study assessed reliability and applicability BPS-NI and the PAINAD-G in a general ward setting. Furthermore, it provides cut-off values in order to estimate pain intensity and support analgesic response.

[Practice of perioperative phantom limb pain prevention in Germany: a nationwide survey]. / Praxis der perioperativen Prävention von Phantomschmerz: eine deutschlandweite Umfrage.

BACKGROUND: The prevalence of phantom limb pain after major amputation remains high and affected patients suffer from relevant impairments in the quality of life. Perioperative treatment strategies may prevent phantom limb pain. This study aims to assess the state of the perioperative anesthesiological pain management for major amputations. Furthermore, it analyzes potentials for optimization and barriers towards a better treatment of patients with amputations. MATERIAL AND METHODS: This online survey was distributed by the German Society of Anesthesiology and Intensive Care Medicine (DGAI) mailing list of anesthesiological consultants. It was approved by the Charité ethics board. RESULTS: Overall, 402 persons participated in this survey. Mostly, general anesthesia (85%), regional anesthesia (63%) and neuraxial anesthesia (49%) were performed in different combinations. Furthermore, 72% of participants reported using i.v. opioids postoperatively, mostly applied via patient-controlled analgesia (PCA). In contrast, preoperative regional anesthesia (74%) and gabapentinoids (67%) were seen as potential methods to improve treatment; however, barrier analysis revealed that treatment options are limited especially by organizational aspects and intrinsic patient factors. CONCLUSION: This survey describes the current practice of phantom limb pain prevention in Germany. It shows an unmet need for specialized perioperative pain treatment. As the evidence regarding treatment recommendations is limited, further research questions can be deduced from this study.

Female Patients with Pneumonia on Intensive Care Unit Are under Risk of Fatal Outcome.

Background and Objectives: The impact of sex on mortality in patients with pneumonia requiring intensive care unit (ICU) treatment is still a controversial discussion, with studies providing heterogeneous results. The reasons for sex differences are widespread, including hormonal, immunologic and therapeutic approaches. This study's aim was to evaluate sex-related differences in the mortality of ICU patients with pneumonia. Material and Methods: A prospective observational clinical trial was performed at Charité University Hospital in Berlin. Inclusion criteria were a diagnosis of pneumonia and a treatment period of over 24 h on ICU. A total of 436 mainly postoperative patients were included. Results: Out of 436 patients, 166 (38.1%) were female and 270 (61.9%) were male. Significant differences in their SOFA scores on admission, presence of immunosuppression and diagnosed cardiovascular disease were observed. Male patients were administered more types of antibiotics per day (p = 0.028) at significantly higher daily costs (in Euros) per applied anti-infective drug (p = 0.003). Mortalities on ICU were 34 (20.5%) in females and 39 (14.4%) in males (p = 0.113), before correcting for differences in patient characteristics using logistic regression analysis, and afterwards, the female sex showed an increased risk of ICU mortality with an OR of 1.775 (1.029-3.062, p = 0.039). Conclusions: ICU mortality was significantly higher in female patients with pneumonia. The identification of sex-specific differences is important to increase awareness among clinicians and allow resource allocation. The impact of sex on illness severity, sex differences in infectious diseases and the consequences on treatment need to be elucidated in the future.

Living with Chronic Pain During the COVID-19 Pandemic: A Qualitative Analysis.

Purpose: COVID-19 pandemic containment measures have led to changes in various areas of life, including restrictions on health care. Patients with chronic pain may have faced an increased burden during pandemic and the resources of this vulnerable population are unknown. Therefore, a qualitative study was conducted to understand how people with chronic pain have experienced the course of the pandemic. Patients and Methods: Twenty semi-structured telephone interviews were conducted six months after the initial lockdown in Germany. The participants were patients with chronic pain who exhibited varying changes in their pain during the first German lockdown, recruited from a German outpatient pain clinic at a Department of Anesthesiology and Intensive Care. The semi-structured interview guidelines were designed to explore how patients with chronic pain experienced their pain during the pandemic, how they coped, and how they experienced pain management during this time. The interview recordings were transcribed verbatim and coded using the qualitative content analysis method. Results: Four themes emerged from the results: differential impact on pain experience, difficulty coping with pain, supportive pain management, and endurance. Conclusion: During this uncertain time, it was particularly important to maintain pain treatment in order to establish a sense of safety and stability. This underscores the special role of maintaining therapeutic contact during a pandemic and the potentially special role of telemedicine.

Local infiltration analgesia versus peripheral nerve block anaesthesia in total knee arthroplasty: a pharmaco-economic comparison.

BACKGROUND: A superior analgesic method in perioperative pain-management of patients receiving total knee arthroplasty is the subject of controversial debate. Although higher cost-efficiency is claimed for the local infiltration analgesia (LIA), there is a lack of data on its costs compared to peripheral nerve block anaesthesia (PNBA). The goal of this study was to investigate the differences in immediate perioperative costs between the LIA and PNBA in treatment of patients receiving total knee arthroplasty. METHODS: The comparison was conducted based on a randomized controlled clinical trial examining 40 patients with elective, primary total knee arthroplasty (TKA, 20 patients with LIA and 20 patients with PNBA). The analysis included surgical case costs, anaesthesiological case costs, material, costs of postoperative opioid requirements and catheter review visits for patients receiving PNBA. RESULTS: The overall mean costs for the LIA-group were 4328.72€ and 4368.12€ for the PNBA (p = 0.851). While there was no statistically significant difference in surgical case costs, the anaesthesiological costs were lower with the LIA procedure (1370.26€ vs. 1542.45€, p = 0.048). Material costs in the LIA group were 4.18€/patient and 94.64€/patient with the PNBA. Costs for postoperative opioid requirements showed no statistically significant difference between the two procedures. CONCLUSIONS: There is no relevant difference in immediate perioperative costs between LIA and PNBA. Shorter induction times lead to lower anaesthesiological case costs with the LIA. Overall economic aspects seem to play a less important role for determining an adequate procedure for perioperative pain management. TRIAL REGISTRATION: The study was approved by the ethics-review-board of Charité Hospital Berlin (Ethikausschuss 4, Charité - Universitätsmedizin Berlin, on 16th February 2017) and registered with data safety authorities. Study patients provided written informed consent to participate in the trial. Study registry: ClinicalTrials.gov, NCT03114306 .

Pneumonia in pediatric critical care medicine and the adherence to guidelines.

BACKGROUND: Different studies in adults reported significant outcome improvement for patients treated with high adherence to guidelines. The present study was initiated to evaluate the impact of adherence to antibiotic prescription guidelines on health outcomes of children on pediatric Intensive Care Unit (PICU) suffering from pneumonia. METHODS: This retrospective cohort study was conducted on a pediatric Intensive Care Unit at Charité Hospital Berlin. All patients with a length of stay (LOS) >24 hours, age <18 years, antimicrobial therapies, and a radiologically confirmed diagnosis of pneumonia according to the "Centers for Disease Control and Prevention" definitions were included during the study period of 2009 and 2010. Adherence to national guidelines was evaluated daily and two groups were defined: Low adherence group (LAG) with a presence of <70% of days with compliant therapy and high adherence group (HAG) with an adherence of ≥70%. RESULTS: High adherence was observed in 65 patients compared with 61 in low-adherence group. Number of patients needing invasive ventilation did not vary between HAG and LAG (N.=37 vs. N.=41; P=0.235). There was a statistically significant shorter duration of ventilation in HAG patients (P=0.031). Time to clinical recovery from pneumonia tended to be shorter in HAG patients (7.5d vs. 10.9d; P=0.07). There was a significant reduction in LOS in HAG patients (9.3d vs. 13.7d; P=0.016). However, mortality appeared comparable between groups. CONCLUSIONS: Similar to previous evidence in adult patients, children with pneumonia seem to benefit from guideline-based antibiotic therapy. Further studies are needed to explore strategies to improve guideline adherence.

Motor and functional outcome of selective dorsal rhizotomy in children with spastic diplegia at 12 and 24 months of follow-up.

BACKGROUND: Selective dorsal rhizotomy (SDR) in ambulatory children affected by cerebral palsy (CP) is a surgical treatment option to lower spasticity and thereby improve gait and ambulation. The aim of the current study is to investigate the outcome of children with respect to spasticity, muscle strength, and overall function after SDR. METHODS: All children who underwent SDR via a single-level laminotomy in the time period from January 2007 to April 2015 at our center were enrolled in this study. Within a standardized evaluation process, the following was assessed routinely pre-operatively and 12 and 24 months following surgery: extent of spasticity at hip adductors and hamstrings as characterized by the Modified Ashworth Scale (MAS), maximal muscle strength as characterized by the Medical Council Research Scale (MRC), overall function regarding ambulation as characterized by the Gross Motors Function Classification System (GFMCS), and overall function as characterized by the Gross Motor Function Measure (GMFM-88). RESULTS: Matching sets of pre- and post-operative assessments of the chosen outcome parameters were available for 109 of the 150 children who underwent SDR within the observation period. After 24 months, the MAS scores of hip adductors (n = 59) improved in 71% and 76% of children on the right and left side, respectively. In 20% and 19%, it remained unchanged and worsened in 9% and 5% of children on the right and left side, respectively (p < 0.00625). For hamstrings, the rates for the right and left sides were 81% and 79% improvement, 16% and 16% unchanged, and 4% and 5% worsened, respectively (p < 0.00625). Muscle strength of ankle dorsiflexion and knee extension significantly improved after 24 months. Overall function assessed by GMFM-88 improved significantly by 4% after 12 months (n = 77) and by 7% after 24 months (n = 56, p < 0.0001). CONCLUSIONS: The presented data underlines the benefit of SDR in a pediatric patient collective with bilateral spastic CP. The procedure resulted in an effective and permanent reduction of spasticity and improved overall function without causing relevant weakness of the lower extremities.

[Cannabis and cannabinoids for the treatment of acute and chronic pain]. / Cannabis und Cannabinoide zur Therapie akuter und chronischer Schmerzen.

Since the Act on the medical use of cannabis, at which cannabis-based medicines and cannabinoids became law, there has been an exponential increase in prescriptions for the acquisition of cannabis for medical purposes. The aim of this leading article is to compile and assess the currently available relevant clinical evidence for the use of cannabis and cannabinoids for treatment of acute and chronic pain. Based on the systematic literature review "Cannabis-Potential and risks (CAPRIS)" commissioned by the German Federal Ministry of Health and the recently published recommendations of the European Pain Federation EFIC, this article aims to give an orientation aid for the decision-making process in the clinical routine.

Time and personnel requirements for antimicrobial stewardship in small hospitals in a rural area in Germany.

BACKGROUND: In order to control their anti-infectives consumption, hospitals are required to provide multidisciplinary teams comprising among others an infectiologist, a microbiologist and a pharmacist. Small hospitals though often do not dispose of the defaulted personnel. This study illustrates a solution for an antimicrobial stewardship program (ASP) in small community hospitals in a rural area in Germany. METHODS: Four hospitals of ca. 200 beds each, jointly hired an antimicrobial stewardship expert to start a common ASP. This expert did rounds on every ward once a week, mostly as chard reviews with the physician in charge. Outside the rounds, he could be consulted by mail. Working time and number of visited patients were documented. Anti-infectives consumption, incidence of Clostridioides difficile infections (CDI) and mortality rates were retrieved from routinely collected data. The intervention period (01/2018-12/2018) was compared to the preintervention period (01/2017-12/2017). RESULTS: 3321 patients were visited in the intervention period. In average, 20 patients were seen per day and 20 min were needed per patient/ chard. About 65% of the expert's working time was needed for rounds, 15% for driving between the hospitals. The anti-infectives consumption of the 4 hospitals in the preintervention period amounted to 50 defined daily doses per 100 occupied bed days. The total consumption was reduced by 10% and of quinolones by 36%. The incidence of hospital-acquired CDI receded from 0.14 to 0.07 cases per 100 patient days (-50%, p = 0.001). The overall in-hospital mortality did not change. CONCLUSIONS: A single expert was able to implement a successfull ASP in 4 hospitals. While multidisciplinary antimicrobial stewardship teams are ideal for tertiary care hospitals, small hospitals need a more practical solution. This survey shows that one expert can be sufficient for several small hospitals even with the distances in a rural setting.

Frequency distribution in intraoperative stimulation-evoked EMG responses during selective dorsal rhizotomy in children with cerebral palsy-part 2: gender differences and left-biased asymmetry.

INTRODUCTION: Spinal reflexes reorganize in cerebral palsy (CP), producing hyperreflexia and spasticity. CP is more common among male infants, and gender might also influence brain and spinal-cord reorganization. This retrospective study investigated the frequency of higher-graded EMG responses elicited by electrical nerve-root stimulation during selective dorsal rhizotomy (SDR), prior to partial nerve- root deafferentation, considering not only segmental level and body side, but also gender. METHODS: Intraoperative neuromonitoring (IOM) was used in SDR to pinpoint the rootlets most responsible for exacerbated stimulation-evoked EMG patterns recorded from lower-limb muscle groups. Responses were graded according to an objective response-classification system, ranging from no abnormalities (grade 0) to highly abnormal (grade 4+), based on ipsilateral spread and contralateral involvement. Non-parametric analysis of data with repeated measures was primarily used in investigating the frequency distribution of these various EMG response grades. Over 7000 rootlets were stimulated, and the results for 65 girls and 81 boys were evaluated, taking changes in the composition of patient groups into account when considering GMFCS levels. RESULTS: The distribution of graded EMG responses varied according to gender, laterality, and level. Higher-graded EMG responses were markedly more frequent in the boys and at lower segmental levels (L5, S1). Left-biased asymmetry in higher-graded rootlets was also more noticeable in the boys and in patients with GMFCS level I. A close link was observed between higher-grade assessments and left-biased asymmetry. CONCLUSIONS: Detailed insight into the patient's initial spinal-neurofunctional state prior to deafferentation suggests that differences in asymmetrical spinal reorganization might be attributable to a hemispheric imbalance.