Regionales Monitoring von Infektionen mittels standardisierter Fallfatalitätsraten am Beispiel von SARS-CoV-2 in Bayern

Hintergrund: Karten zur zeitlichen Entwicklung der regionalen Verteilung einer gesundheitsbezogenen Maßzahl ermöglichen public-health-relevante Bewertungen des Gesundheitsgeschehens. Ziel der Arbeit: Die Arbeit führt das Konzept der standardisierten Fallfatalitätsrate (sFFR) ein. Sie beschreibt das Verhältnis der regionalen Abweichung in der Mortalität zur regionalen Abweichung im dokumentierten Infektionsprozess. Die regionalen sFFR-Werte werden in Karten dargestellt und die darin beobachtete zeitlich variierende regionale Heterogenität interpretiert. Materialien und Methoden: Die regionale sFFR ist der Quotient der regionalen standardisierten Mortalitäts- und Fallrate. Sie wird mittels eines bivariaten Modells geschätzt. Die in Karten dargestellten sFFR-Werte basieren auf den SARS-CoV-2-Meldedaten aus Bayern seit Anfang April 2020 bis Ende März 2021. Es werden 4 Quartale (Q2/20, Q3/20, Q4/20, Q1/21) betrachtet. Ergebnisse: In den betrachteten Quartalen liegen die bayerischen naiven FFR-Werte bei 5,0 %, 0,5 %, 2,5 % und 2,8 %. In Q2/20 sind die regionalen sFFR-Werte unregelmäßig über das Bundesland verteilt. Diese Heterogenität schwächt sich in der zweiten Welle der Epidemie ab. In Q1/21 zeigen sich in Südbayern nur vereinzelt Regionen mit erhöhter sFFR (> 1,25). Im Norden Bayerns bilden sich Cluster von Regionen mit einer sFFR > 1,25. Das Oberallgäu ist die Region mit dem niedrigsten sFFR-Wert (0,39, 95 % Kredibilitätsintervall: 0,25–0,55). Diskussion: In Bayern zeigen sich heterogene regionale SARS-CoV-2-spezifische sFFR-Werte, die sich über die Zeit verändern. Sie schätzen das relative Risiko, als dokumentierter Infektionsfall an/mit COVID-19 zu versterben. Eine starke kleinräumige Variabilität der sFFR legt nahe, regionale gegenüber übergeordneten Maßnahmen zur Steuerung des Infektionsgeschehens vorzuziehen

Area Deprivation and COVID-19 Incidence and Mortality in Bavaria, Germany: A Bayesian Geographical Analysis

Background: Area deprivation has been shown to be associated with various adverse health outcomes including communicable as well as non-communicable diseases. Our objective was to assess potential associations between area deprivation and COVID-19 standardized incidence and mortality ratios in Bavaria over a period of nearly 2 years. Bavaria is the federal state with the highest infection dynamics in Germany and demographically comparable to several other European countries. Methods: In this retrospective, observational ecological study, we estimated the strength of associations between area deprivation and standardized COVID-19 incidence and mortality ratios (SIR and SMR) in Bavaria, Germany. We used official SARS-CoV-2 reporting data aggregated in monthly periods between March 1, 2020 and December 31, 2021. Area deprivation was assessed using the quintiles of the 2015 version of the Bavarian Index of Multiple Deprivation (BIMD 2015) at district level, analyzing the overall index as well as its single domains. Results: Deprived districts showed higher SIR and SMR than less deprived districts. Aggregated over the whole period, the SIR increased by 1.04 (95% confidence interval (95% CI): 1.01 to 1.07, p = 0.002), and the SMR by 1.11 (95% CI: 1.07 to 1.16, p < 0.001) per BIMD quintile. This represents a maximum difference of 41% between districts in the most and least deprived quintiles in the SIR and 110% in the SMR. Looking at individual months revealed clear linear association between the BIMD quintiles and the SIR and SMR in the first, second and last quarter of 2021. In the summers of 2020 and 2021, infection activity was low. Conclusions: In more deprived areas in Bavaria, Germany, higher incidence and mortality ratios were observed during the COVID-19 pandemic with particularly strong associations during infection waves 3 and 4 in 2020/2021. Only high infection levels reveal the effect of risk factors and socioeconomic inequalities. There may be confounding between the highly deprived areas and border regions in the north and east of Bavaria, making the relationship between area deprivation and infection burden more complex. Vaccination appeared to balance incidence and mortality rates between the most and least deprived districts. Vaccination makes an important contribution to health equality

Psychiatric Comorbidity and Stress in Medical Students Using Neuroenhancers

Background: Pharmacological neuroenhancement (PN) is a common healthcare problem at least among students. PN seems to be associated with stressful situations. There is a lack of data about personal characteristics, comorbidities, and coping strategies regarding stress and factors of resilience in students and medical staff. Methods: A web-based survey about the non-medical use of PN drugs with a focus on neuroenhancement was developed and distributed among medical students throughout Germany; the questionnaire was open in April and May of 2020. The survey contained questions about the use of well-known PN drugs, frequency, special purposes, reasons for the use, psychiatric disorders, use of psychotropic drugs apart from PN purposes, and factors of resilience using the brief resilience scale. Results: Data of 1,159 students of medicine were analyzed. The most frequently used substances for PN were coffee (78.8% lifetime prevalence rate), energy drinks (45.7%), caffeine tablets (24.3%), methylphenidate (5.2%), illicit amphetamines (2.0%), and cocaine (1.7%). 98.4% suspected that PN drug use could lead to addiction. PN drug use specifically for PN was significantly associated with the use of (a) any psychotropic drug (other than neuroenhancers), (b) any psychiatric disorder, and (c) higher values of feeling pressure to perform in professional/students' life and in private life as well as (d) the subjective feeling of pressure to perform to be burdening and (e) harmful to one's own health. PN drug use in general was significantly associated with being less resilient. The use of illicit PN drugs, over the counter drugs and prescription drugs was associated with being less resilient. Conclusion: This study indicates that PN with legal and illegal drugs is a widespread phenomenon among German medical students. Users seem to be more often burdened by psychiatric disorders, especially addictive disorders, the perception of stress, pressure to perform and low levels of resilience. These aspects should be considered in further investigation of PN drug use

Efficacy and Safety of Approved First-Line Tyrosine Kinase Inhibitor Treatments in Metastatic Renal Cell Carcinoma: A Network Meta-Analysis

Introduction This network meta-analysis aims to deliver an up-to-date, comprehensive efficacy and toxicity comparison of the approved first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC) in order to provide support for evidence-based treatment decisions. Previous NMAs of first-line mRCC treatments either predate the approval of all the first-line TKIs currently available or do not include evaluation of safety data for all treatments. Methods We performed a systematic literature review and network meta-analysis of phase II/III randomised controlled trials (RCTs) assessing approved first-line TKI therapies for mRCC. A random effects model with a frequentist approach was computed for progression-free survival (PFS) data and for the proportion of patients experiencing a maximum of grade 3 or 4 adverse events (AEs). Results The network meta-analysis of PFS demonstrated no significant differences between cabozantinib and either sunitinib (50 mg 4/2), pazopanib or tivozanib. The network meta-analysis indicated that in terms of grade 3 and 4 AEs, tivozanib had the most favourable safety profile and was associated with significantly less risk of toxicity than the other TKIs. Conclusion These network meta-analysis data demonstrate that cabozantinib, sunitinib, pazopanib and tivozanib do not significantly differ in their efficacy, but tivozanib is associated with a more favourable safety profile in terms of grade 3 or 4 toxicities. Consequently, the relative toxicity of these first-line TKIs may play a more significant role than efficacy comparisons in treatment decisions and in planning future RCTs

Regional deep hyperthermia: quantitative evaluation of predicted and direct measured temperature distributions in patients with high-risk extremity soft-tissue sarcoma

Background: Temperature distributions resulting from hyperthermia treatment of patients with high-risk soft-tissue sarcoma (STS) were quantitatively evaluated and globally compared with thermal simulations performed by a treatment planning system. The aim was to test whether the treatment planning system was able to predict correct temperature distributions. Methods: Five patients underwent computed tomography (CT) fluoroscopy-guided placement of tumor catheters used for the interstitial temperature measurements. For the simulations, five 3 D patient models were reconstructed by segmenting the patient CT datasets into different tissues. The measured and simulated data were evaluated by calculating the temperature change (ΔT), T90, T50, T20, Tmean, Tmin and Tmax, as well as the 90th percentile thermal dose (CEM43T90). In order to measure the agreement between both methods quantitatively, the Bland–Altman analysis was applied. Results: The absolute difference between measured and simulated temperatures were found to be 2°, 6°, 1°, 4°, 5° and 4 °C on average for Tmin, Tmax, T90, T50, T20 and Tmean, respectively. Furthermore, the thermal simulations exhibited relatively higher thermal dose compared to those that were measured. Finally, the results of the Bland–Altman analysis showed that the mean difference between both methods was above 2 °C which is considered to be clinically unacceptable. Conclusion: Given the current practical limitations on resolution of calculation grid, tissue properties, and perfusion information, the software SigmaHyperPlan™ is incapable to produce thermal simulations with sufficient correlation to typically heterogeneous tissue temperatures to be useful for clinical treatment planning

CXCL13 and CXCL9 CSF Levels in Central Nervous System Lymphoma-Diagnostic, Therapeutic, and Prognostic Relevance

Background: Diagnostic delay and neurologic deterioration are still a problem for the treatment of rapidly progressing CNS lymphoma (CNSL); there is an unmet need for a diagnostic test with a high diagnostic yield and limited risk, minimizing the time to the initiation of effective treatment. Methods: In this prospective monocentric study, we analyzed the utility of CXCL13 and CXCL9 as diagnostic, therapeutic and prognostic biomarkers for CNSL. Cerebrospinal fluid (CSF) from 155 consecutive patients admitted with brain lesions of various origins was collected. Levels of CXCL13 and CXCL9 were analyzed by ELISA. Additionally, CSF was analyzed during CNSL disease course (relapse, remission, progress) in 17 patients. Results: CXCL13 and CXCL9 CSF levels were significantly increased in patients with CNSL compared to control patients with lesions of other origin. Using logistic regression and a minimal-p-value approach, a cut-off value of 80 pg/ml for CXCL13 shows high sensitivity (90.7%) and specificity (90.1%) for the diagnosis of active CNSL. CXCL9 at a cut-off value of 84 pg/ml is less sensitive (61.5%) and specific (87.1%). Both cytokines correlate with the clinical course and response to therapy. Conclusions: Our results confirm the excellent diagnostic potential of CXCL13 and introduce CXCL9 as a novel albeit less powerful marker for PCNSL

Just “Like Coffee” or Neuroenhancement by Stimulants?

Introduction: Pharmacological neuroenhancement (PN) is a topic of increasing importance and prevalence among students. However, there is a lack of differentiating PN substances, according to their psychoactive effects. In particular, there is a lack of data about PN by caffeinated drinks, even if coffee is a common and broadly used Neuroenhancer because of its cognitively enhancing effects regarding wakefulness, alertness and concentration. Materials and Methods: A web-survey was developed for German students and alumni about the non-medical use of caffeine for PN contained questions about coffee, caffeinated drinks and energy drinks, caffeine pills and methylxanthine tea regarding frequency and further contextual factors. Results: Six hundred and eighty-three participants completed the survey. Nearly all participants knew about PN (97.7%). 88.1% admitted using some over-the-counter substances. For PN purposes, coffee was used by 72.9% followed by energy drinks (68.2%) and cola drinks (62.4%). Methylxanthine containing tea was used for PN purposes, too (black tea 52.3%, green tea 51.7%). 1.8% admitted using illegal substances or prescription drugs, too. Discussion: Using legal methylxanthine containing drinks for PN seems to be extremely common with coffee and energy drinks being the preferred substances, while illegal and prescription drugs are only minimally used. Further studies should investigate the awareness of methylxanthine containing drinks as well as its character to be a flavoring drink or a neuroenhancer

Treatment outcome, cognitive function, and psychopathology in methamphetamine users compared to other substance users

BACKGROUND: The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group. Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited. Due to specific characteristics of methamphetamine users, the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well. We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances. AIM: To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes. METHODS: A total of 110 subjects were recruited for an observational, longitudinal study from a German inpatient addiction treatment center: 55 patients with methamphetamine dependence and 55 patients with dependence of other substances (“OS group”). Both groups were examined at beginning (baseline) and end of treatment (after 6 mo) with regard to treatment retention, craving, cognitive functioning, psychosocial resources, personality traits, depression, and other psychiatric symptoms. Instruments used were Raven’s IQ test, Mannheimer craving scale, cognitrone cognitive test battery, NEO personality factors inventory, Hamilton depression scale, Becks depression inventory, and a symptom checklist. The statistical methods used were χ(2)-test, t-test and multiple mixed ANOVAs. RESULTS: A total drop-out rate of 40% (methamphetamine-group: 36.4%; OS-group: 43.6%) was observed without significant differences between groups. At baseline, methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient, fewer years of education, slower working speed, and decreased working accuracy, as well as less cannabinoid and cocaine use. Methamphetamine-group subjects further showed a significantly lower score of conscientiousness, depressive, and psychiatric symptoms than subjects from the OS-group. In both groups, a reduction of craving and depressive symptoms and an improvement of working speed and working accuracy was noted after treatment. CONCLUSION: There are differences between methamphetamine users and users of other drugs, but not with regard to the effectiveness of treatment in this inpatient setting. There are differences in cognitive function and psychopathology between methamphetamine and other drugs users. The existing treatment options seem to be an effective approach in treating methamphetamine dependence