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A periodic arrangement of chains of gold disks shows pronounced plasmonic grating resonances. These have a clear impact on the surface enhanced Raman-scattering (SERS) signal from 4-methylbenzenethiol molecules, which form self-assembled monolayers on the gold surface: Besides a clear polarization dependence, the SERS-spectra also exhibit a maximum when the excitation laser wavelength matches the plasmonic grating resonance. These features are explained by a combined near and far field coupling of the individual plasmonic dipoles allowing the design of optimized nanostructures for effective SERS substrates in the future. [ABSTRACT FROM AUTHOR]

The debate on South Africa's strategic minerals should continuously be evaluated. Three matters are addressed. First, the existing literature on South Africa's strategic minerals lacks clarity as far as the concept “strategic value” is concerned. This shortcoming is addressed by applying Critchley's conceptualization to the South African situation. Second, we argue that the interdependence between supplier and consumer—in this case South Africa and the U.S.—will remain dominant. Third, how will a change in relations affect perceptions of strategic value? For example, will a regime change in South Africa (either a reactionary Conservative Party government or a radical African National Congress government) influence the scarcity of, dependency on, or access to strategic minerals? For this purpose eight future scenarios are discussed. For each a situational analysis is made and its effects on strategic value are outlined. [ABSTRACT FROM PUBLISHER]

Background: A large prospective multicenter cohort study with systematic follow-up recently reported a 2.3% 2-year cumulative incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE)., Objectives: The present investigation aimed to determine the reported prevalence and incidence of CTEPH diagnosis after acute PE in real-world practice over a 12-year period., Methods: This study was based on nationwide ambulatory billing claims and drug prescription data of all residents with public health insurance in Germany from 2010 to 2021., Results: A total of 573 972 patients with acute PE (median age, 71 years; 57.4% women) were identified between 2010 and 2021. Prevalence of CTEPH among patients with history of PE increased during the period from 0.4% in 2010 to 0.9% in 2021. CTEPH was diagnosed in 2556 patients after acute PE, with most (17.6%) diagnoses reported within the first 3 months after the index PE event. The cumulative incidence rate after 3 months (first quarter) was calculated at 0.08% and after the first 2 years (eighth quarter) at 0.36%; it was 0.75% over the entire (90-month) follow-up period. Patients with CTEPH diagnosis during follow-up more often had right ventricular dysfunction at the index acute PE (14.9% vs 8.3%; P < .001)., Conclusion: The low CTEPH incidence rate after acute PE in the present analysis suggests low awareness of CTEPH. It further suggests a lack of systematic follow-up protocols for acute PE survivors in the real world. Improved implementation of existing recommendations on follow-up strategies after PE is warranted., Competing Interests: Declaration of competing interests L.H. received lecture/consultant fees from Johnson & Johnson, Inari Medical, MSD, and Boston Scientific, outside the submitted work. L.M.P. reports no conflict of interest. I.F. declares no conflict of interest. S.B. received lecture/consultant fees from Bayer HealthCare, Concept Medical, BTG Pharmaceuticals, INARI, Boston Scientific, and LeoPharma; institutional grants from Boston Scientific, Bentley, Bayer HealthCare, INARI, Medtronic, Concept Medical, Bard, and Sanofi; and economic support for travel/congress costs from Daiichi Sankyo, BTG Pharmaceuticals, and Bayer HealthCare, outside the submitted work. S.P. reports no conflict of interest. T.M. reports no conflict of interest. S.K. reports institutional grants and personal lecture/advisory fees from Bayer AG, Daiichi Sankyo, and Boston Scientific; institutional grants from Inari Medical; and personal lecture/advisory fees from MSD and Bristol-Myers Squibb/Pfizer. K.K. reports no conflict of interest. M.B. reports no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Adverse drug reactions (ADRs) are known to show sex-specific differences in occurrence and phenotype. The aim of this study was to analyse sex-specific differences in ADR-drug combinations that required hospitalization based on two different datasets., Methods: We performed a complementary analysis of (i) spontaneously reported (n = 12 564, female = 51.7%) and (ii) systematically collected ADR reports from a prospective multicentre observational study (ADRED, n = 2355, female = 48.2%) from Germany in the ADR database EudraVigilance (EV). Both datasets were analysed separately concerning the suspected drugs, ADRs and ADR-drug combinations more frequently reported for females or males by calculating reporting odds ratios (ROR) with 95% confidence intervals. ADR-drug combinations more frequently reported for either females or males in EV reports were related to prescription data. Finally, the results from both datasets were discussed with regard to their (dis-)concordance., Results: In both datasets, some antineoplastic agents and nervous system drugs were found to be reported more often for females than males (RORs ranging from 1.5 [1.1-2.1] for quetiapine in spontaneous reports to 41.3 [13.1-130.0] for trastuzumab in spontaneous reports). ADRs of the respiratory system, and haemorrhages were described predominantly for males in both datasets. In spontaneous reports the ADR-drug combination self-injurious behaviour-quetiapine was more often reported for females without and with consideration of drug prescriptions (ROR: 3.8 [1.3-11.0]). Quetiapine and psychiatric disorders (superordinate level) was exclusively reported for females in ADRED reports., Conclusions: Our results can contribute to raise awareness and further knowledge regarding sex-specific ADRs. The findings require further in-depth investigation., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: We aimed to provide an update on trends in antipsychotic (AP) use among children and adolescents in Germany., Materials and Methods: Based on nationwide outpatient claims data from Germany, we conducted a cross-sectional study. For each year from 2011 to 2020, we determined the prevalence of AP use, defined as the proportion of children and adolescents with at least one AP dispensation. We evaluated trends in AP use by age, sex, and AP class (typical vs. atypical). Additionally, we assessed trends in the specialty of AP prescribers and the frequency of psychiatric diagnoses among AP users., Results: Overall, data from more than 12 million children and adolescents were included for each calendar year (2011: 12,488,827; 2020: 13,330,836). From 2011 to 2020, the overall prevalence of pediatric AP use increased from 3.16 to 3.65 per 1,000, due to an increase in use of both typical APs (from 1.16 to 1.35 per 1,000) and atypical APs (from 2.35 to 2.75 per 1,000). The largest increase in AP use was found among 15- to 19-year-old females, with an increase from 3.88 per 1,000 in 2011 to 7.86 per 1,000 in 2020 (+103%), mainly due to rising quetiapine use (from 1.17 to 3.46 per 1,000). Regarding prescribers' specialty, the proportion of APs prescribed by child and adolescent psychiatrists increased during the studied period (2011: 24.8%; 2020: 36.4%), whereas prescriptions by pediatricians (2011: 26.0%; 2020: 19.9%) and general practitioners (2011: 18.0%; 2020: 12.4%) decreased. Risperidone was the most commonly used AP in males, and quetiapine was the leading AP in females, each with the highest prevalence in 15- to 19-year-olds. In male risperidone users in this age group, the most frequent diagnosis was attention-deficit/hyperactivity disorder (50.4%), while in female quetiapine users it was depression (82.0%)., Discussion: Use of APs among children and adolescents in Germany has continued to increase over the last decade. The sharp increase in AP use among 15- to 19-year-old females, which is largely due to an increased use of quetiapine, is remarkable. Potential reasons for this increase-e.g., limited access to psychosocial treatments-should be carefully analyzed. Also, the introduction of more restrictive prescribing guidelines might be considered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dörks, Bachmann, Below, Hoffmann, Paschke and Scholle.)

Background: The current uptake of many vaccinations recommended for persons aged 60 and older is unsatisfactory in Germany. Lack of confidence in the safety and efficacy of vaccinations, lack of knowledge and insecurities about possible side effects, and numerous pragmatic barriers are just some of the reasons to be mentioned. General practitioners (GPs) play a central role in the vaccination process. Therefore, effective interventions in this context are needed to address the various barriers and improve the vaccination uptake rates., Methods: A complex intervention will be implemented and evaluated in 1057 GPs' practices in two German federal states. The components include trainings for GPs and medical assistants on communication psychology, medical aspects, and organisational vaccination processes. The primary outcome influenza vaccination rate and the secondary outcomes vaccination uptake rate of other vaccinations as well as vaccine literacy of patients will be examined. The intervention will be evaluated in a mixed methods study with a controlled design. Survey data will be analysed descriptively and by using mean comparisons as well as multivariable multilevel analyses. The qualitative data will be analysed with qualitative content analysis. The secondary data will be analysed by using descriptive statistics, a pre-post comparison by performing mean comparisons, cluster analysis, and subgroup analyses., Discussion: In this study, a complex intervention to improve vaccination rates in GP practices for the vaccinations recommended for people aged 60 years and older will be implemented and evaluated. Additionally, improvements in patients' vaccine-related health literacy and knowledge, and patients' intention to get vaccinated are expected. The mixed methods design can deliver results that can be used to improve preventive health care for elderly people and to gain more knowledge on vaccination uptake and the intervention's effectiveness., Trial Registration: Trial registration number: DRKS00027252 (retrospectively registered)., (© 2023. The Author(s).)

The aim of the study was to examine whether the COVID-19 pandemic had any effect on antibiotic prescription rates in children in Germany. Using the nationwide outpatient prescription data from the Statutory Health Insurance from 2010 to 2021, changes in the monthly prescriptions of systemic antibiotics dispensed to children aged 0-14 years were examined ( n = 9,688,483 in 2021). Interrupted time series analysis was used to assess the effect of mitigation measures against SARS-COV-2, introduced in March and November 2020, on antibiotic prescription rates. In the pre-pandemic period, the antibiotic prescription rates displayed a linear decrease from 2010 to 2019 (mean annual decrease, -6%). In 2020, an immediate effect of mitigation measures on prescription rates was observed; in particular, the rate decreased steeply in April (RR 0.24, 95% CI: 0.14-0.41) and November 2020 (0.44, 0.27-0.73). The decrease was observed in all ages and for all antibiotic subgroups. However, this effect was temporary. Regionally, prescription rates were highly correlated between 2019 and 2020/2021. Substantial reductions in antibiotic prescription rates following the mitigation measures may indicate limited access to medical care, changes in care-seeking behavior and/or a decrease of respiratory infections. Despite an all-time low of antibiotic use, regional variations remained high and strongly correlated with pre-pandemic levels., Competing Interests: The authors declare no conflicts of interest.

Understanding associations between chronic pain and health outcomes among detoxification patients may help improve treatment outcomes and abstinence rates. Exercise is a modifiable lifestyle factor that may reduce the effect of pain on outcomes in this population. The current study examined whether baseline pain, exercise, and their interaction were associated with psychiatric and medical severity, and abstinence self-efficacy, over six months following detoxification. Participants were veteran patients in alcohol or opioid detoxification treatment (N = 298) who were followed for six months (91.1%). Psychiatric severity and abstinence self-efficacy improved over the six months after detoxification; medical severity was stable. More intense pain at baseline was associated with poorer psychiatric and medical outcomes during the post-detoxification period. Regular exercise at baseline was associated with less psychiatric severity and more abstinence self-efficacy during the post-detoxification period. A significant pain by exercise interaction at baseline indicated that regular exercise was associated with more abstinence self-efficacy during the post-detoxification period only among participants with less intense pain. Pain by exercise interactions was not significant for the outcomes of psychiatric and medical severity. Among detoxification patients, exercise may be beneficial in improving outcomes among those with less intense pain., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Breast cancer is a heterogeneous disease that can be subdivided into unique molecular subtypes based on protein expression of the Estrogen Receptor, Progesterone Receptor, and/or the Human Epidermal Growth Factor Receptor 2. Therapeutic approaches are designed to inhibit these overexpressed receptors either by endocrine therapy, targeted therapies, or combinations with cytotoxic chemotherapy. However, a significant percentage of breast cancers are inherently resistant or acquire resistance to therapies, and mechanisms that promote resistance remain poorly understood. Notch signaling is an evolutionarily conserved signaling pathway that regulates cell fate, including survival and self-renewal of stem cells, proliferation, or differentiation. Deregulation of Notch signaling promotes resistance to targeted or cytotoxic therapies by enriching of a small population of resistant cells, referred to as breast cancer stem cells, within the bulk tumor; enhancing stem-like features during the process of de-differentiation of tumor cells; or promoting epithelial to mesenchymal transition. Preclinical studies have shown that targeting the Notch pathway can prevent or reverse resistance through reduction or elimination of breast cancer stem cells. However, Notch inhibitors have yet to be clinically approved for the treatment of breast cancer, mainly due to dose-limiting gastrointestinal toxicity. In this review, we discuss potential mechanisms of Notch-mediated resistance in breast cancer cells and breast cancer stem cells, and various methods of targeting Notch through γ-secretase inhibitors, Notch signaling biologics, or transcriptional inhibitors. We also discuss future plans for identification of novel Notch-targeted therapies, in order to reduce toxicity and improve outcomes for women with resistant breast cancer.

Telehealth interventions have the potential to deter repeated detoxification episodes and improve outcomes. Using a sample of 298 detoxification inpatients, this randomized controlled trial compared Enhanced Telephone Monitoring (ETM) to usual care (UC) on the primary outcome of reducing subsequent detoxification, and secondary outcomes of linking patients to addiction treatment and mutual-help, and patients' experience of improved substance use and mental health outcomes. At the 3-month follow-up (i.e., at the end of the ETM intervention), compared to UC patients, ETM patients were significantly less likely to have received additional inpatient detoxification, but no more likely to have participated in 12-step groups or received outpatient addiction treatment. Even so, ETM patients had better alcohol, drug, and mental health outcomes. In contrast, at the 6-month follow-up, patients in ETM and UC generally did not differ on primary or secondary outcomes. Findings suggest that ETM deters additional detoxification episodes while the intervention is ongoing, but not after the intervention ends. Because telephone monitoring is low-intensity and low-cost, its extension over time may help reduce repeated detoxifications., (Published by Elsevier Inc.)

Although completion of detoxification (detox) and a successful transition from detox to substance use disorder (SUD) treatment and/or mutual-help groups are associated with better SUD outcomes, many patients do not complete detox or do not receive SUD care following detox. The purpose of this structured evidence review, summarizing data extraction on a yield of 26 articles, is to identify patient, program, and system factors associated with the outcomes of completion of alcohol detox and successful transitions from alcohol detox to SUD treatment and mutual-help group participation. The review found wide variability among studies in the rates at which patients complete a detox episode (45 to 95%) and enter SUD treatment or mutual-help groups after detox (14 to 92%). Within program factors, behavioral practices that contribute to both detox completion and transitioning to SUD care after detox entail involving the patient's family and utilizing motivational-based approaches. Such practices should be targeted at younger patients, who are less likely to complete detox. Although more studies using a randomized controlled trial design are needed, the evidence suggests that barriers to detox completion and transition to SUD care can be overcome to improve patient outcomes., (Published by Elsevier Inc.)

After a first irradiation with 2 and 5 Gy blood samples were collected at 30 minutes' intervals for 24 hours in 19 tongue cancer patients to assess the activity of the glycosis enzyme glucose-6-phosphate isomerase (GPI) and the creatine kinase (CK). In all patients the GPI activity exhibited peaks at reproducible points in time. Observed for the very first time, this GPI peak had a height at 15 to 18 hours following radiation that correlated with the tumor volume and the irradiation dose. We refer to it as the oncoradiogenic enzyme peak. The frequency of the appearance of a late enzyme peak is significantly related to the presence of regional lymph node metastases. The radiobiological considerations regarding the potential causes for such post-irradiation increases in enzyme activity are discussed. The impact of demonstrating oncoradiogenic GPI peaks for optimizing radiotherapy is outlined.

In 43 patients with oesophageal, pancreatic and rectal carcinoma blood samples were taken after the first irradiation and the activity of the glycolytic enzyme glucose-6-phosphate isomerase was measured. In all patients GPI peaks occurred at reproducible time intervals. The height of the enzyme peak occurring 15.5 to 19.5 hours p.irr. was significantly dependent on tumour size and irradiation dose. The frequency of a late occurring enzyme peak was dependent on the presence of regional lymph node metastases. Possible sources of the enzyme peaks are discussed from a radiobiological point of view and the meaning of such enzyme peaks for the optimization of radiation therapy is pointed out.

In 20 patients with oesophageal carcinoma blood samples were taken after the first irradiation and the activity of the glycolytic enzyme glucose-6-phosphate isomerase was measured. In all patients there occur GPI peaks at reproducible times. The height of the enzyme peak occurring 15.5 to 19.5 hours p.irr. expresses a significant dependence on tumour size and irradiation dose. The frequency of a late occurring enzyme peak depends on the appearance of regional lymph node metastases. Possible sources of the enzyme peaks are discussed from a radiobiological point of view and the meaning of such enzyme peaks for the optimization of radiation therapy is pointed out.

Blood samples were taken from 39 patients with head and neck carcinomas after the initial irradiation, and the activity of the glycolytic enzyme glucose-6-phosphate isomerase (GPI) was measured. All patients showed GPI peaks at reproducible times. The height of the enzyme peak occurring 15.5-19.5 h after irradiation, was significantly correlated with tumour size and histological tumour differentiation. A late enzyme peak was associated with regional lymph node metastases. Possible sources of the enzyme peaks are discussed from a radiobiological point of view, and the value of such enzyme peaks for the optimization of radiation therapy is pointed out.

Following the first irradiation with a dose of 1.6 respectively 2 Gy we determined the activity of glucose-6-phosphate isomerase (GPI) and of creatine kinase in intervals of 30 minutes for 24 hours. In all patients we could observe peaks of GPI-activity 15.5 to 19.5 hours after irradiation corresponding to tumour volume and grading. Frequency depends on present lymph node metastases detected by lymphography and/or computed tomography. Possible reasons have been discussed by the viewpoint of radiation biology and the meaning with respect to an optimal radiation treatment.

With the development of the state of medical knowledge in the special subjects and the increase of medicamentous and physiotherapeutic possibilities the indications of radiotherapy of benign nontumourous diseases changed. The application of radiotherapy altogether decreased in benign diseases. In tabular form the basic rules radiation technique of benign diseases, the indications and possibilities as well as the contraindications of the radiotherapy of benign non-tumourous diseases are described. Own experiences and evaluations confirm that the radiotherapy, for instance in acute parotitis, axillary hidradenitis, degenerative changes of the skeleton, kelloid revisions or chronic pancreatitis is an effective, rapidly acting and economic form of therapy. The knowledge about the possibilities and limits of the radiotherapy of benign non-tumourous diseases belongs to the speciality of internal medicine.