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Coming dissertations at MedFak

  • The Monoamine Oxidase A Gene and Antisocial Outcomes : An Examination of Genetic, Epigenetic, and Environmental Factors Author: David Checknita Link: Publication date: 2021-02-23 10:04

    Background. Antisocial behaviour involves violation of the basic rights of others or social norms or rules. Such behaviours are indexed in diagnoses such as conduct disorder (CD) in adolescence and antisocial personality disorder (ASPD) in adulthood, which are typified by comorbidity with mood, anxiety, and substance misuse disorders. Alcohol misuse is strongly associated with antisocial behaviour and persistent aggressive behaviours. How environmental and biological factors interface to modulate risk for these outcomes is not yet understood, however, the interaction of adversity with a variable number tandem repeat (uVNTR) polymorphism of the monoamine oxidase gene A (MAOA) gene associates with antisocial behaviour and mental disorders. Further, DNA methylation in a region of interest (ROI) spanning MAOA’s first exonic/intronic junction associates with ASPD in men as well as other mood, anxiety, and substance misuse disorders. 

    Aim and Methods. We characterized methylation of the MAOA ROI by sex and age and examined how negative and positive environmental factors interact with MAOA genotype and methylation on antisocial phenotypes and mental disorders. Participants included men and women from a clinical population of young adults recruited in adolescence at a substance misuse clinic and a community sample of adolescents. 

    Findings. (1) Sex but not age was associated with methylation levels such that high methylation levels among women likely represent X-chromosome inactivation, and sexual abuse was associated with hypermethylation of the MAOA first exon, (2) high methylation levels mediated associations between sexual abuse and current depression diagnosis in women, (3) the highest levels of aggressive behaviour were found among maltreat male carriers of the low-expressing MAOA-uVNTR allele and displayed high levels of exonic methylation, while no interactions were shown in women, and (4) among adolescent girls, but not boys, positive parent-child relationship attenuated the interaction of maltreatment and the high-expressing MAOA-uVNTR allele on alcohol consumption, though the interactions were not robust to adjustments for tobacco use, substance misuse, and delinquent behaviours.

    Conclusion. The findings presented here advance our understanding of how maltreatment interfaces with genotypic and epigenetic factors, in a sex-dependent manner, to promote aggressive behaviour and mental disorders among susceptible individuals.


  • Antibiotic Resistance: A Multimethod Investigation of Individual Responsibility and Behaviour Author: Mirko Ancillotti Link: Publication date: 2021-02-17 09:48

    The rapid development of antibiotic resistance is directly related to how antibiotics are used in society. The international effort to decrease and optimise the use of antibiotics should be sustained by the development of policies that are sensitive to social and cultural contexts.

    The overarching aim of the thesis was to explore and discuss the Swedish public’s beliefs, values and preferences influencing engagement in judicious antibiotic behaviour.

    Study I explored through focus group discussions lay people’s perceptions and beliefs about antibiotics and antibiotic resistance. The Health Belief Model was used to identify factors that could promote or hinder engagement in judicious antibiotic behaviour. Participants found antibiotic resistance to be a serious problem but were not equally worried about being affected by it. There was a tension between individual and collective reasons for engaging in judicious behaviour.

    Study II explored lay people’s views on the moral challenges posed by antibiotic resistance through focus group discussions. Participants identified in the decreasing availability of effective antibiotics a problem of justice, which involves individual as well as collective moral responsibility. Different levels of policy demandingness were discussed in light of these results.

    Study III investigated, through an online Discrete Choice Experiment, public preferences regarding antibiotic treatment and the relative weight of antibiotic resistance in decision-making. Public behaviour may be influenced by concerns over the rise of antibiotic resistance. Therefore, stressing individual responsibility for antibiotic resistance in clinical and societal communication may affect personal decision-making.

    Study IV clarified the notions of collective and individual moral responsibility for antibiotic resistance and suggested a virtue-based account thereof. While everyone is morally responsible for minimising his/her own contribution to antibiotic resistance, individuals do or do not engage in judicious antibiotic behaviour with different degrees of voluntariness.

    The findings suggest that people could change their behaviour due to concerns over their own contribution to antibiotic resistance. Effective health communication should be developed from an appraisal of people’s attitudes, beliefs and social norms that influence antibiotic resistance related behaviours. Policy demandingness should take into account socioeconomic factors characterising local realities. 

  • Medication reviews by clinical pharmacists in older hospitalised patients : Implementation, performance and effects Author: Thomas G. H. Kempen Link: Publication date: 2021-02-11 13:40

    Background Inappropriate use of medications is a leading cause of avoidable harm in health care. Medication reviews by clinical pharmacists improve medication use, but evidence on hard clinical outcomes in older hospitalised patients is scarce and implementation in practice is challenging. The aim of this thesis was to study the implementation, performance and effects of medication reviews by clinical pharmacists in older hospitalised patients.

    Methods A case study explored the factors involved in the implementation and sustainability of medication reviews by clinical pharmacists in Region Uppsala, Sweden. A pragmatic multicentre cluster-randomised crossover trial (MedBridge) was conducted to study the effects of hospital-based comprehensive medication reviews (CMRs) including post-discharge follow-ups on older patients’ healthcare utilisation, compared with only hospital-based reviews and usual care. The primary outcome measure was the incidence of unplanned hospital visits within 12 months. A process evaluation was conducted alongside the trial, for which different methods were applied: semi-structured interviews with patients and healthcare professionals, intervention fidelity assessment and process outcomes assessment. A practical tool to identify medication-related hospital admissions, one of the trial’s secondary outcomes, was developed and validated.

    Results Multiple factors involved in the implementation and sustainability of medication reviews by clinical pharmacists were identified. Examples of facilitating factors were a national focus on quality of care for the elderly and clinical pharmacy education. In total, 2637 participants (median age 81 years) were included in the MedBridge trial. The primary outcome measure did not differ between the treatment groups. Analysis of the interviews with patients and healthcare professionals resulted in seven and six themes, respectively, that were related to the performance of the trial’s interventions. A recurrent theme was the unclear role and responsibilities of the ward-based pharmacist. The intervention fidelity was high during hospital admission and lower surrounding discharge. In 77% of the intervention patients, at least one medication discrepancy or drug-related problem was solved. The developed tool, AT-HARM10, was deemed valid for use by pharmacy students to identify medication-related admissions in older patients.

    Conclusions This thesis suggests that, despite a high percentage of patients with medication discrepancies or drug-related problems being solved, hospital-based CMRs with and without post-discharge follow-ups, as conducted in the MedBridge trial, do not decrease the incidence of unplanned hospital visits in older patients. Future research and clinical initiatives may benefit from addressing the factors related to the implementation and performance of medication reviews that were identified in this thesis.