Background: COVID-19 and antimicrobial resistance (AMR) are two intersecting public health crises. Antimicrobial overuse in patients with COVID-19 threatens to contribute to the growing threat of AMR. Guidelines are fundamental in encouraging antimicrobial stewardship. We sought to assess the quality of antibiotic prescribing guidelines and recommendations in the context of COVID-19, and if these guidelines incorporate principles of antimicrobial stewardship. Methods: We performed a systematic survey which included a search using the concepts “antibiotic/antimicrobial” in September to November 2022 of the eCOVID-19 living map of recommendations (RecMap) which aggregates and summarizes guidelines across a range of international sources and all languages. Guidelines providing explicit recommendations regarding antibacterial use in COVID-19 from any jurisdiction were eligible for inclusion. Guideline and recommendation quality were assessed using the AGREE II and AGREE-REX instruments, respectively. We extracted guideline characteristics including panel representation and the presence or absence of explicit statements related to antimicrobial stewardship (i.e., judicious antibiotic use, antimicrobial resistance or adverse effects as a consequence of antibiotic use). We used logistic regression to evaluate the relationship between guideline characteristics including quality and incorporation of antimicrobial stewardship principles. Results: Twenty-eight guidelines with 63 antibiotic prescribing recommendations were included. Recommendations focused on antibiotic initiation (n=52, 83%) and less commonly antibiotic selection (n=13, 21%), and duration of therapy (n=15, 24%). Guideline and recommendation quality varied widely. Twenty (71%) guidelines incorporated at least one concept relating to antimicrobial stewardship. Including infectious diseases expertise on the guideline panel (OR 9.44, 97.5%CI: 1.09 to 81.59) and AGREE-REX score (OR 3.26, 97.5%CI: 1.14 to 9.31 per 10% increase in overall score) were associated with a higher odds of guidelines addressing antimicrobial stewardship. Conclusion: There is an opportunity to improve antibiotic prescribing guidelines in terms of both quality and incorporation of antimicrobial stewardship principles. These findings can help guideline developers better address antibiotic stewardship in future recommendations beyond COVID-19. / Thesis / Master of Public Health (MPH) / COVID-19 and antimicrobial resistance (AMR) are two serious threats to public health. Inappropriate use of antibiotics in patients with COVID-19 can worsen AMR and make future infections harder to treat. Practice guidelines can help healthcare providers prescribe antibiotics wisely. Using antibiotics carefully to reduce their harms is called antibiotic stewardship. This study evaluated the quality of practice guidelines for antibiotic prescribing in patients with COVID-19. It also assessed if the guidelines included principles of antibiotic stewardship. We searched for guidelines in a database called the eCOVID-19 living map of recommendations (RecMap). We found 28 guidelines with 63 recommendations. Identified guidelines differed widely in quality. Just over two-thirds of guidelines addressed antibiotic stewardship. Guidelines developed along with infectious disease experts and guidelines with higher recommendation quality scores were more likely to address antibiotic stewardship. Our findings can help guideline developers better address antibiotic stewardship in future recommendations.

Depression ist auch bei Älteren eine häufige Erkrankung und kann für die Betroffenen schwere Folgen haben. Durch den Demographischen Wandel wird der Anteil älterer Menschen an der Bevölkerung in den nächsten Jahren zunehmen, wodurch das Thema Altersdepression noch wichtiger werden wird. Obwohl es etablierte und wirksame Therapiemethoden für depressive Episoden auch im hohen Alter gibt, werden Depressionen gerade in dieser Bevölkerungsgruppe häufig nicht erkannt und den Patienten somit der Zugang zu einer wirksamen Behandlung verwehrt. Deshalb wird in einigen Ländern bereits ein generelles Screening auf Depressionen empfohlen, jedoch noch nicht in Deutschland. Um Screening Methoden effektiv und ressourcenschonend einzusetzen, ist es wichtig Untergruppen von Patienten zu identifizieren, die besonders anfällig für Depressionen sind. Kenntnisse über Risikofaktoren von Depressionen im Alter sind essentiell, um solche Untergruppen eingrenzen zu können. In den letzten Jahrzehnten wurden eine große Anzahl von Studien zu Risikofaktoren von Altersdepression durchgeführt. Jedoch wiesen viele dieser Arbeiten schwerwiegende methodische Mängel auf oder es handelte sich um Querschnittstudien. Um ein tieferes Verständnis über diese Risikofaktoren zu ermöglichen, führten wir zwei Studien durch: Zunächst fasten wir alle Längsschnittstudien zu Risikofaktoren für Depressionen bei Personen im Alter von 65 Jahren oder älter in einem systematischen Review zusammen, die strenge Qualitätsstandards erfüllten. Anschließend führten wir eine hochqualitative Längsschnittstudie zu Risikofaktoren von Depressionen in einer großen Kohorte älterer Menschen im Alter von mindestens 75 Jahre durch. In die endgültige Analyse unserer systematische Übersichtsarbeit schlossen wir 30 Längsschnittstudien mit ein, in welchen multivariate Analysemethoden angewendet und strenge Einschlusskriterien erfüllt wurden. Diese Übersichtsarbeit konnte einen guten Überblick über qualitativ hochwertige Studien zu Risikofaktoren der Depression im Alter verschaffen. Jedoch konnten wir aufgrund der Heterogenität der eingeschlossenen Studien, insbesondere im Bereich der eingeschlossenen Faktoren und der verwendeten Erhebungsmethoden der Faktoren, sowie dem hohen Verzerrungsrisiko, keine Metaanalyse durchführen. In unserer prospektiven Kohortenstudie analysierten wir Risikofaktoren sowie Inzidenzraten von Depressionen in einer repräsentativen Stichprobe von 3.327 älteren Erwachsenen, die über 13 Jahre nachbeobachtet wurden. Als statistische Methode wendeten wir aufgrund der hohen Sterblichkeit der Teilnehmer die statistische Methode der Competing Risk Regression an. Die Studienteilnehmer wurden aus Hausarztpraxen rekrutiert. 2.436 Patienten ohne signifikante depressive Symptome zu Studienbeginn wurden in die endgültige Analyse miteingeschlossen. Von diesen entwickelten 543 (22,2 %) signifikante depressive Symptome (Inzidenzrate 38,8 pro 1000 Personenjahre (95 % KI 35,5–42,4)). Durch unsere Analyse, in der Versterben der Studienteilnehmer als konkurrierendem Ereignis einberechnet wurde, ergaben sich folgende Risikofaktoren für das Auftreten von depressiven Symptomen: Weibliches Geschlecht, der Beziehungsstatus ledig oder geschieden, subjektiver Gedächtnisverlust mit und ohne Sorgen über diesen, Sehstörungen, sowie Einschränkungen in der körperlichen Mobilität. Die konsistentesten Risikofaktoren in allen Studien, einschließlich unserer eigenen prospektiven Studie, waren Mobilitätseinschränkungen, gefolgt von Sehstörungen. Die meisten untersuchten Faktoren ergaben in verschiedenen Studien widersprüchliche Ergebnisse. Auch wenn diese Dissertation keine abschließenden Ergebnisse in Form einer Metaanalyse liefern konnte, zeigt sie doch mögliche Wege auf, um in zukünftigen Studien zu Risikofaktoren für Depressionen in der älteren Bevölkerung verlässlichere und konsistentere Ergebnisse zu erhalten. Auf diese Weise könnten Gruppen mit hohem Risiko für depressiven Episode in dieser unterdiagnostizierten und unterbehandelten Population identifiziert und ein Screening für Hochrisikogruppen etabliert werden. Da die Folgen einer Depression schwerwiegend sind und wirksame Behandlungsmöglichkeiten zur Verfügung stehen, lohnt es sich, die Forschung zu Risikofaktoren für Depressionen bei älteren Menschen zu verfeinern und fortzuführen.

Introduction: Patients with autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) show more symptoms of ADHD. Since there are more adverse events caused by psychostimulants compared to non-psychostimulants, the use of a non-psychostimulant such as atomoxetine might prove more beneficial for younger patients and/or those with comorbid ADHD. Objective: The aim of this thesis is to determine the efficacy and tolerability of atomoxetine in ASD patients presenting with ADHD, by examining (a) differences in ADHD symptoms for participants receiving atomoxetine versus those receiving placebos, and (b) risk differences in adverse events between these participants. Methods: An electronic search of both PubMed.gov and ClinicalTrials.gov were conducted. To be deemed eligible, studies had to (a) be randomized, double-blind, placebo-controlled trials comparing atomoxetine with a placebo, (b) administer atomoxetine for at least 1 week, and (c) include data on either ADHD outcomes or adverse events. Effect sizes for ADHD outcomes were calculated using Cohen's d, whereas risk differences were calculated for adverse events. For each of these two meta-analyses, effect sizes were aggregated across studies using a random effects method. Results: Overall ADHD outcomes were better for participants who received atomoxetine than for participants who received placebo, =0.297. Participants who received atomoxetine also demonstrated better outcomes in terms of attention and hyperactivity-impulsivity symptoms, =0.345 and 0.393, respectively. Though there were more adverse events for patients taking atomoxetine than placebo, the results were not statistically significant. Discussion: This thesis extends the findings of previous meta-analyses of pharmacological treatments for ASD and ADHD, while addressing the concerns raised in the critique of existing meta-analyses presented in this thesis, e.g., limited studies, length of treatment weeks, and dichotomization of data. It provides evidence that atomoxetine improves ADHD symptoms, with an overall frequency of adverse events that did not sufficiently differ from placebo beyond chance.

Background: Global health is a complex, interdisciplinary, and contested field. It is rapidly growing and undergoing ideological and methodological changes. Despite many theoretical claims over what global health research ought to be, there are few empirical reports on what global health is, as a present field of research. The aim of this study is to: 1) determine patterns in global health research, based on key research characteristics; and 2) determine relationships between these characteristics to identify and define conceptual frameworks in global health research. Methodology: A systematic review of research in global health journals was conducted for papers published in the years 2010, 2015, and 2020. Categorical data on 17 research characteristics was extracted from all studies included in the analysis. The relationships between these characteristics was analyzed and visualized using multiple correspondence analysis, as implemented in the R’s ca package. Significance tests of independence determined relationships between pairs of variables. Results: The final analysis was done on 1033 included studies from 14 journals. 56% of the studies used a quantitative observational methodology. While 82% of research had at least one author affiliated with a high-income country, 96% of research funded (at least partially) by the Bill & Melinda Gates Foundation had at least one author affiliated with a high-income country. There was a significant relationship between the use of social and structural determinants of health and the authors’ affiliations (X2=59.06, p < 0.001), with the use of social and structural determinants of health lower among lower-income authors than high-income authors. The first and second dimensions of multiple correspondence analysis explained 38% of the variables’ deviation from independence. Conclusion: Multiple correspondence analysis offers a novel way of understanding global health research, contributing empirical data to the discourse on what lies ahead for the field of global health. The relationship between the use of social and structural determinants of health, authorship, and research methodologies point to the need for important conversations on the direction of global health research, starting from where we are at now. / Thesis / Master of Science (MSc) / While the importance of the field of global health is more prominent than ever, it is a field of uncertainty, controversy, contested merit, and often disreputable history. Conversations abound on the strengths and weaknesses of the field and what needs to change; yet, there is a lack of empirical grounding for these discussions. In this study, I reviewed global health research literature, identifying 17 key characteristics that surface in theoretical conversations on global health, and scored 1033 global health research studies according to these characteristics. Using multiple correspondence analysis, the 17 characteristics were analyzed together and visualized to elucidate the relationships between the characteristics. I found that: over half of the studies were quantitative observational; most research in global health had at least one author from a high-income country; and middle-income authors were less likely to study social and structural determinants of health than high-income authors. These findings lend important empirical evidence to conversations on the direction of the field, starting from where we are at now.

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