Thesis (M.Med. ( Anaesthesiology)) --University of Limpopo (Medunsa Campus), 2011 / Introduction: Multiple studies have described a variable incidence of transient hearing loss (hypoacousis) from 0.4% to 40% after subarachnoid block, especially in the low-frequencies range (125 – 500 Hz) (1, 2). The mechanism of transient hypoacousis is attributed to leakage of cerebrospinal fluid, which leads to a decrease in perilymph pressure within the cochlear. Hypothesis: The study hypothesis was based on an assumption that hearing loss is more frequent in young patients who undergo spinal anaesthesia in comparison with elderly patients. Objective: 1) To determine the incidence of hearing loss after spinal anaesthesia in the young versus elderly patients. Materials and Methods: Ninety-eight male patients (ASA 1 - 11) scheduled for cystoscopy under spinal anaesthesia were recruited for the study. Recruitment of patients for the study was age dependent and was divided into two groups: One group (49 patients) had patients aged between 17 and 44 years (Group Y) and the other group had 49 patients aged between 45 and 77 years made up group two (GROUP E). Subarachnoid injection at L3-4 was performed using a standard 22-gauge Quincke spinal needle with patients in the sitting position and 2,5 ml to 3 ml of 0.5% isobaric bupivacaine was administered. Patients were evaluated on the day before spinal anaesthesia by pure tone audiometry at three different frequency sounds viz. 125 – 500 Hz (Low frequency), 500 – 2000 Hz (Speech frequency) and at 2000 – 4000 Hz (High frequency). This assessment was repeated 48 hours after the spinal block was given Statistical Analysis: Analysis was descriptive providing information on the mean (or median) and standard deviation of the variables for each of the two groups. The results of the audiometry were analyzed using repeated measures analysis of variance and transformation to p-value. Differences in outcomes of the study between the two groups were recorded as being statistically significant if p-value is ≤ 0.05. Results: No patient from the two groups developed hearing loss either at low or high frequencies. However, there was a statistically significant improvement in audiometric results (p-value ranging from 0.0001 and 0.063) 48 hours post-surgery in the elderly group as compared with patients in the younger group. Conclusion: The study revealed no hearing loss post-spinal anaesthesia in both groups. It did, however, show that the elderly group have better hearing acuity at all three frequency levels of sound compared to the younger group after spinal anaesthesia

Background Malaria remains a serious epidemic threat in the Lowveld region of Mpumalanga Province. In order to appropriately target interventions to achieve substantial reductions in malaria morbidity and mortality, there is a need to assess the impact of current control interventions such as indoor residual spraying (IRS) for vector control. This study aimed to assess long-term changes in the burden of malaria in Mpumalanga Province during the past eight years (2001-2009) and whether IRS and climate variability had an effect on these changes. Methods All malaria cases and deaths notified to the Malaria Control Programme, Department of Health was reviewed for the period 2001 to 2009. Data were retrieved from the provincial Integrated Malaria Information System (IMIS) database. Climate and population data were obtained from the South Africa Weather Service and Statistics South Africa, respectively. Descriptive statistics were computed to determine any temporal changes in malaria morbidity and mortality. Autoregressive integrated moving average (ARIMA) models were developed to assess the effect of climatic factors on malaria. Results Within the eight-year period of the study, a total of 35,191 cases and 164 deaths-attributed to malaria were notified in Mpumalanga Province. There was a significant decrease in the incidence of malaria in Mpumalanga Province from 385 in 2001/02 to 50 cases per 100,000 population in 2008/09 (P < 0.005). The overall incidence and case fatality rates were 134 cases per 100,000 and 0.54%, respectively. Malaria incidence and case fatality rate by gender showed significant differences, higher in males than in L.M. Ngomane University of Pretoria, 2012 iv females (166.9 versus 106.4; P < 0.001; CFR 0.41% versus 0.55%). The incidence of malaria increased from age 5-14 years (70), reaching a peak at age 25-34 years (190), declining thereafter (50 in those >65 years). Mortality due to malaria was higher in those >65 years, the mean CFR reaching a 2.1% peak. Almost half (47.8%) of the notified cases originated from Mozambique and Mpumalanga Province itself constituted 50.1%. The distribution of malaria varied across the districts, highest in Ehlanzeni district (96.5%), lowest in Nkangala (<1%) and Gert Sibande (<1%). A notable decline in malaria case notification was observed following the increased IRS coverage from 2006/07 to 2008/09 malaria seasons. A distinct seasonal transmission pattern was found to be significantly related to changes in rainfall patterns (P = 0.007). Conclusion Decades of continuous IRS with insecticides have proved to be successful in reducing the burden of malaria morbidity and mortality in Mpumalanga Province between 2001 and 2009. A decline of above 50% in malaria morbidity and mortality was observed following expanded IRS coverage. These results highlight the need to continue with IRS together with other control strategies until interruption in local malaria transmission is completely achieved and alternative vector control strategies implemented. Efforts need to be directed towards the control of imported cases, interruption of local transmission and focus on research into sustainable and cost-effective combination of control interventions. / Dissertation (MSc)--University of Pretoria, 2012. / School of Health Systems and Public Health (SHSPH) / Unrestricted

Aim: The aim of the study was to analyse the injuries and illnesses in Swedish Para athletes during four Paralympic Games (PG), 2012-2018. The research questions (RQ) were: 1) what was the injury incident rate (IR), and which anatomical areas were affected by injuries? 2) what was the illness IR and which physiological systems were affected by illnesses? 3) did the injury and illness IR differ between the Swedish delegation and the reference group (RG), where most athletes participating in the four PGs were included? 4) were there any associations between injury and illness IR and subgroups of athletes? Method: A retrospective analysis of data from a large ongoing prospective study of injuries and illnesses initiated by the International Paralympic Committee in 2012. Data from 157 Swedish Paralympic athletes were analysed and compared to previous results from the RG.  For RQ1, 2 and 3, injuries and illnesses were reported as IR, calculated per 1000 athlete days, in the Swedish delegations (RQ1-3) and compared to the RG (RQ3). For RQ4, a univariate logistic regression analysis was conducted to find possible associations between risk of injury and illness, and subgroups. Results: The injury IR in Swedish athletes varied between the four PGs, from 2.5 to 59.5 per 1000 athlete days. Most injuries occurred in the upper limb. There was a particularly high occurrence of injuries in Para ice hockey players. The illness IR varied from 3.6 per 1000 athlete days in London (2012), to 39.5 in Sochi (2014). The respiratory tract was most affected by illness, in both Swedish athletes and the RG. Most injuries and illnesses in the Swedish delegation were acute onset, but only a minority led to days lost from training and competition. The Swedish delegation had a lower injury IR per 1000 athlete days compared to the RG in all PGs, except for Pyeongchang (2018), where they had an almost three times higher IR. The illness IR for the Swedish delegation was, compared to the RG, lower in London (2012), the same in Rio (2016) and higher in both Sochi (2014) and Pyeongchang (2018). Participation in the Winter Games was associated with a higher risk for both injury and illness compared to the Summer Games. There was also an increased risk of injury for athletes in a contact sport compared to a non-contact sport. Conclusions: This thesis indicates that there is a need to continue monitoring Para athletes, both during and between competitions, to get more knowledge about injury and illness incidence patterns, as well as preventable risk factors. The latter would be especially important for Para ice hockey. It is yet to see if the awareness of the importance of hygiene measures and physical distancing to reduce spreading of infections, brought on by the Covid-19 pandemic, will affect the occurrence of respiratory tract infections during large sporting events.

Introduktion Alpin skidåkning är en populär men skadedrabbad vinteridrott som varit en olympisk gren sedan 1936. Idrotten består av fyra grenar: Slalom, Storslalom, Super-G och Störtlopp. I Sverige finns det möjlighet för ungdomar att specialisera sig inom sin idrott i samband med gymnasiet, där de kan kombinera studier med idrott. Allvarliga skador har visats påverka individuella idrottares rankingpoäng och karriärer. Syftet med denna studie var dels att undersöka skadeförekomsten mellan årskurser och kön vid Sveriges alpina skidgymnasium och dels vilken typ av skada som var mest förekommande. Metod En enkät skickades ut till sammanlagt 116 elever vid Sveriges alpina skidgymnasium varav 87 av dessa (40 män respektive 47 kvinnor i åldern 16–20 år) valde att delta i studien. Resultat Resultatet av enkätundersökningen visar att 64 % av skadorna i studien rapporterades av kvinnor och 36 % rapporterades av män. Studien visade en låg skillnad i träningsmängd och sömn mellan män och kvinnor. Av totalt 53 akuta och belastningsrelaterade skador var 40 % ryggskador. Av alla svarande uppgav 53 % att de någon gång under nuvarande läsår (2020–2021) tränat med smärta eller i behov av behandling. Resultatet visar också att årskurs 2 hade störst procentuell skadeförekomst med 81 % under nuvarande läsår.  Slutsats Baserat på skadorna som rapporterats i studien skulle män och kvinnor möjligen gynnas av att ha olika träningsupplägg. Ett mer aktivt jobb med skadeprevention kan behövas med tanke på att 61 % av deltagarna varit skadade minst en gång senaste läsåret. Bättre kommunikation mellan tränare och elever gällande träning med besvär kan behövas.    Nyckelord: Skadeförekomst, Idrottsgymnasium, Träningsbelastning / Introduction Alpine skiing is a popular winter sport that is often associated with injury. It has been part of the winter Olympics since 1936 and is categorized into four different disciplines; Slalom, Giant Slalom, Super G and Downhill. Young athletes in Sweden have the opportunity to specialize in alpine skiing as they start high school, where they can combine studies with sports. Severe injuries can significantly affect individual athletes’ ranking points and careers. The purpose of this study was to investigate which injury is the most common and the difference in injury incidence between the sexes and first to fourth grade at Swedish Alpine High Schools. Method A questionnaire was sent out to students at Sweden's Alpine Ski High School, of which 87 students (40 men and 47 women aged 16–20) chose to participate in the study.  Results Of all injuries in the study, 64 % were reported by women and 36 % by men. The study only showed a slight difference in sleeping patterns and training volume between the sexes. Out of 53 reported acute and overuse injuries, 40 % were back injuries. Of all the participants 53 % claimed they had exercised while in pain or need of treatment during the previous year. Second grade had the highest injury incidence, with 81 % during the previous year. Conclusion Based on the injuries reported in the study, men and women would most likely benefit from personalized training programs. A more effective job with injury prevention could be needed considering 61 % of the participants have been injured at least once during the previous year. Better communication between coaches and students about training with pain or in need of treatment might be required.   Keywords: Incidence of injury, Sports High School, Training load

Hintergrund: Weltweit berichteten zahlreiche Studien von einer steigenden Inzidenz von Patienten mit angeborenen Bauchwanddefekten. Besonders die Zahl der Gastroschisis-Kinder hat deutlich zugenommen. Auch die Neonatologen der Universitätsklinik Leipzig beschrieben ein gehäuftes Auftreten von Patienten mit Gastroschisis und Omphalocele. Aufgabe der vorliegenden Arbeit war es, die Inzidenz dieser beiden Fehlbildungen am Universitätsklinikum Leipzig zu ermitteln und zu untersuchen, wie sich die Fallzahlen während des Untersuchungszeitraumes (1998-2008) entwickelt hatten. Zudem sollten Parameter identifiziert werden, die die Prognose der betroffenen Kinder bis zur Entlassung beeinflussten. Ein weiteres Anliegen dieser Studie war es, mithilfe einer ausführlichen Literaturrecherche, einen Überblick über die aktuelle Behandlung und Prognose der beiden Fehlbildungen zu geben. Methoden: Im Rahmen einer retrospektiven Untersuchung erfolgte die Erhebung und Auswertung der Daten von 27 Kindern mit Gastroschisis sowie 19 Kindern mit Omphalocele, die zwischen 1998 und 2008 in der Universitätsklinik Leipzig behandelt wurden. Mithilfe des Mann-U-Whitney-Tests sowie des exakten Tests nach Fisher wurden zahlreiche Merkmale hinsichtlich ihrer Auswirkungen auf das Outcome überprüft. Als Parameter, die das Outcome widerspiegelten, galten der Beginn des enteralen Kostaufbaus mit Tee-Glucose-Lösung und Milch, die Dauer der parenteralen Nährstoffzufuhr und des Krankenhausaufenthaltes, sowie Nachoperationen, Komplikationen und die Letalität während des stationären Aufenthaltes. Ergebnisse: An der Universitätsklinik Leipzig betrug die Inzidenz von Gastroschisis 14 pro 10 000 Lebendgeburten und von Omphalocele 9 pro 10 000 Lebendgeburten. Die Inzidenz blieb während des elfjährigen Beobachtungszeitraumes konstant. Der Vergleich früh- und reifgeborener Gastroschisis-Patienten zeigte, dass eine Frühgeburt weder mit einem früheren Beginn der oralen Ernährung mit Tee-Glucose-Lösung (11 d vs. 14 d; p nicht signifikant) und Milch (17 d vs. 17 d; p nicht signifikant), noch mit einer Verkürzung der parenteralen Ernährung (36 d vs. 37 d; p nicht signifikant) und stationären Behandlung (48 d vs. 50 d; p nicht signifikant) einherging. Häufig verkomplizierten Infektionen (12/27) und sekundäre Darmverschlüsse (9/27) mit der Notwendigkeit einer zusätzlichen Operation den postoperativen Verlauf der Gastroschisis-Patienten. Letztgenannte Komplikation führte zu einer erheblich protrahierten parenteralen Ernährung (79 d vs. 31 d; p < 0,05) und stationären Behandlung (101 d vs. 38 d; p < 0,05), während Infektionen kaum Auswirkungen auf das Outcome hatten. Es zeigte sich, dass vorrangig Kinder mit kleinem Defekt (<= 4 cm) sowie mit prolabiertem Magen einen Ileus entwickelten. Neben Darmverschlüssen führten intestinale Begleitfehlbildungen tendenziell zu einer Verlängerung der Hospitalisierungszeit (73 d vs. 48,5 d; p nicht signifikant). Gelang die orale Zufuhr von Milch innerhalb der ersten 14 Lebenstage, so verringerte sich die Dauer der parenteralen Ernährung (30 d vs. 37 d; p < 0,05) und der stationären Behandlung (41 d vs. 67 d; p nicht signifikant). Bei Patienten mit Omphalocele bestimmten vor allem die Größe der Omphalocele, der Inhalt des Bruchsackes sowie der Zeitpunkt des oralen Ernährungsbeginns die Prognose. Ein großer (> 4 cm) Bauchwanddefekt ging mit einer erhöhten Infektionsrate (4/7 vs. 1/11; p < 0,05), prolongierten parenteralen Nahrungszufuhr (26 d vs. 17 d; p < 0,05) sowie stationären Behandlung (46 d vs. 24 d; p nicht signifikant) einher. Extraintestinale Begleitanomalien zeigten sich jedoch häufiger bei Patienten mit kleinem Defekt (5/11 vs. 1/7; p nicht signifikant). Befand sich die Leber außerhalb der Abdominalhöhle, waren zusätzliche Fehlbildungen seltener (3/11 vs. 5/7; p < 0,05). Eine prolabierte Leber verzögerte tendenziell die parenterale Ernährung (24 d vs. 18 d; p nicht signifikant) und die Krankenhausverweildauer (46 d vs. 21 d; p nicht signifikant). Ein frühzeitiger Beginn des enteralen Kostaufbaus mit Milch innerhalb der ersten zehn Lebenstage führte hingegen zu einer Verkürzung der parenteralen Ernährung (17 d vs. 27 d; p < 0,05) und stationären Behandlung (22,5 d vs. 49 d; p nicht signifikant). Schlussfolgerung: Die Inzidenz von Gastroschisis und Omphalocele blieb während des Beobachtungszeitraumes konstant. Die Prognose der Gastroschisis-Patienten wurde durch eine Frühgeburt nicht verbessert, so dass eine Termingeburt angestrebt werden sollte. Die Daten der vorliegenden Arbeit legen nahe, dass ein frühzeitiger Nahrungsaufbau mit der oralen Zufuhr von Tee ab dem achten Lebenstag sowie Milch ab dem zehnten Lebenstag günstig für das Outcome hinsichtlich der Dauer der parenteralen Ernährung und des stationären Aufenthaltes ist. Darmverschlüsse stellten schwerwiegende Komplikationen dar und verschlechterten das Outcome maßgeblich. Eine große Omphalocele sowie eine ausgetretene Leber erhöhten die Morbidität. Ebenso wie bei Gastroschisis-Kindern scheint ein frühzeitiger Beginn der enteralen Ernährung das Outcome der Omphalocele-Patienten hinsichtlich der Dauer der parenteralen Ernährung und Krankenhausbehandlung zu verbessern. Deshalb empfehlen wir ab dem fünften sowie siebten Lebenstag die enterale Ernährung mit Tee sowie Milch zu beginnen. Ein großes Manko der vorliegenden Studie ist die kleine Fallzahl dieser retrospektiven, monozentrischen Erhebung. Zur besseren Erfassung der Patienten mit angeborenen Bauchwanddefekten und um aussagekräftige epidemiologische und prognostische Ergebnisse zu erhalten, bedarf es eines Fehlbildungsregisters in Sachsen, so wie es bereits in anderen Bundesländern angewandt wird.:INHALTSVERZEICHNIS BIBLIOGRAPHISCHE BESCHREIBUNG II INHALTSVERZEICHNIS III ABBILDUNGSVERZEICHNIS V TABELLENVERZEICHNIS VI ABKÜRZUNGSVERZEICHNIS VIII 1. EINLEITUNG 1 1.1. Gastroschisis 1 1.1.1. Historie 1 1.1.2. Pathogenese und Ätiologie 2 1.2. Omphalocele 4 1.2.1. Historie 4 1.2.2. Pathogenese und Ätiologie 5 1.3. Fragestellungen und Ziele dieser Studie 6 2. MATERIAL UND METHODEN 8 2.1. Patientengut 8 2.2. Datenerhebung 8 2.3. Versorgung der Patienten in der Universitätsklinik Leipzig 9 2.4. Statistische Auswertung 10 3. ERGEBNISSE 11 3.1. Ergebnisse der Literaturrecherche 11 3.1.1.Gastroschisis 11 3.1.1.1. Pränatale Diagnostik 11 3.1.1.2. Assoziierte Fehlbildungen 13 3.1.1.3. Geburtszeitpunkt und -modus 14 3.1.1.4. Operatives und stationäres Management 16 3.1.1.5. Komplikationen und Mortalität 17 3.1.1.6. Langfristige Ergebnisse 19 3.1.2. Omphalocele 20 3.1.2.1. Pränatale Diagnostik 20 3.1.2.2. Assoziierte Fehlbildungen 21 3.1.2.3. Geburtsmodus 21 3.1.2.4. Operatives und stationäres Management 22 3.1.2.5. Komplikationen und Mortalität 24 3.1.2.6. Langfristige Ergebnisse 25 3.2. Ergebnisse der Daten der Universitätsklinik Leipzig 27 3.2.1. Gastroschisis 27 3.2.1.1. Allgemeine Daten des untersuchten Kollektivs 27 3.2.1.2. Daten zur Untersuchung des Verlaufs und des Outcomes 29 3.2.1.3. Outcomeanalyse 37 3.2.1.4. Zusammenfassung der Ergebnisse 53 3.2.2. Omphalocele 54 3.2.2.1. Allgemeine Daten des untersuchten Kollektivs 54 3.2.2.2. Daten zur Untersuchung des Verlaufs und des Outcomes 56 3.2.2.3. Outcomeanalyse 65 3.2.2.4. Zusammenfassung der Ergebnisse 77 4. DISKUSSION 78 4.1. Gastroschisis 78 4.2. Omphalocele 87 4.3. Stärken und Schwächen der Untersuchung 91 4.4. Empfehlungen zur Behandlung Neugeborener mit angeborenen Bauchwanddefekten 92 4.4.1. Gastroschisis 92 4.4.2. Omphalocele 94 5. ZUSAMMENFASSUNG 95 6. LITERATURVERZEICHNIS 98 7. EIGENSTÄNDIGKEITSERKLÄRUNG 125 8. LEBENSLAUF

Pain symptoms in aging populations have significant public health impact. The aim of this study was to determine risk factors for the incidence of pain in older adults, focusing on those factors that can be modified. Secondary analyses were performed of survey data from the nationally representative Health and Retirement Study of US adults older than 50 years. Generalized estimating equations logistic regressions were used to evaluate the effect of selected variables on the incidence of pain using biennial (1992 through 2006) data, determining the relationship between the incidence of pain and the potential risk factors. Of the 18,439 survey respondents in 2006, 34.1% (95% CI: 33.2%, 35.0%) reported that they were often troubled by pain; 24.3% reported having moderate to severe pain; and 22.3% reported that their daily life was affected by pain. Between 1992 and 2006, 7967 individuals reported new onset of pain in 169,762 person-years of follow-up, an incidence of 4.69 (4.59, 4.80) per 100 person-years. Depression and being overweight were independent predictors associated with an increased likelihood of incident pain. Current smoking increased the likelihood of incident pain only in those subjects who also reported depression. In conclusion, pain is a common symptom in older adults. Depression, smoking, and overweight are potentially modifiable risk factors and could be considered in the prevention and management of pain in older adults.

Background: The objective of this study was to establish a prospective population-based cohort to investigate the prevalence, incidence and risk factors for mild cognitive impairment (MCI) and dementia. Methods: The Olmsted County, Minn., population, aged 70-89 years on October 1, 2004, was enumerated using the Rochester Epidemiology Project. Eligible subjects were randomly selected and invited to participate. Participants underwent a comprehensive in-person evaluation including the Clinical Dementia Rating Scale, a neurological evaluation and neuropsychological testing. A consensus diagnosis of normal cognition, MCI or dementia was made by a panel using previously published criteria. A subsample of subjects was studied via telephone interview. Results: Four hundred and two subjects with dementia were identified from a detailed review of their medical records but were not contacted. At baseline, we successfully evaluated 703 women aged 70-79 years, 769 women aged 80-89 years, 730 men aged 70-79 years and 517 men aged 80-89 years (total n = 2,719). Among the participants, 2,050 subjects were evaluated in person and 669 via telephone. Conclusions: Strengths of the study are that the subjects were randomly selected from a defined population, the majority of the subjects were examined in person, and MCI was defined using published criteria. Here, we report the design and sampling, participation, baseline measures and sample characteristics.

We carried out a population-based study on low-grade diffuse gliomas in the Canton of Zurich, Switzerland (population 1.16 million). From 1980 to 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 122 (12.4%) were low-grade (WHO grade II). The incidence rates adjusted to the World Standard Population, per million population per year, were 2.28 for low-grade diffuse astrocytomas, 0.89 for oligoastrocytomas, and 2.45 for oligodendrogliomas. The survival rate (mean follow-up 7.5±4.8 years) was highest for patients with oligodendroglioma (78% at 5 years, 51% at 10 years), followed by those with oligoastrocytoma (70% at 5 years, 49% at 10 years) and fibrillary astrocytoma (65% at 5 years, 31% at 10 years). Survival of patients with gemistocytic astrocytoma was poor, with survival rates of 16% at 5 years and 0% at 10 years. Younger patients (<50 years) survived significantly longer than older patients (>50 years; P=0.013). DNA sequencing, performed in 84% of cases, revealed that TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but were infrequent (13%) in oligodendrogliomas. The presence of TP53 mutations was associated with shorter survival of patients with low-grade diffuse gliomas (log-rank test; P=0.047), but when each histological type was analyzed separately, an association was observed only for oligoastrocytoma (P=0.05). Loss on 1p and 19q were assessed by quantitative microsatellite analysis in 67% of cases. These alterations were frequent in oligodendrogliomas (1p, 57%; 19q, 69%), less common in oligoastrocytomas (lp, 27%; 19q, 45%), rare in fibrillary astrocytomas (lp, 7%; 19q, 7%), and absent in gemistocytic astrocytomas. None of these alterations were predictive of survival. These results establish the frequency of key genetic alterations in low-grade diffuse gliomas at a population-based level. Multi-variate Cox's regression analysis indicates that only age and histological type, but not genetic alterations, are significant predictive factors.

This diploma thesis is focused on examining the impacts of the distribution of the tax burden/benefit on the seller and the buyer in the changes of the VAT rates for foodstuffs in the countries of the European Union, between years 2010 and 2016. The main objective of the work is to set relative values of the tax incidence for consumers and producers in the individual EU countries, and then to deter-mine the general model of this distribution. For the solution, the tax impact meas-urement method was used at the time of the tax rate change using formulas. It was found that in the EU countries the average tax burden on the buyer was 66%. The buyer also receives an average tax benefit of 58% on average. This finding is beneficial for tax policy makers in their decision making.

Indiana University-Purdue University Indianapolis (IUPUI) / Observational studies and clinical trials with time-to-event data frequently involve multiple event types, known as competing risks. The cumulative incidence function (CIF) is a particularly useful parameter as it explicitly quantifies clinical prognosis. Common issues in competing risks data analysis on the CIF include interval censoring, missing event types, and left truncation. Interval censoring occurs when the event time is not observed but is only known to lie between two observation times, such as clinic visits. Left truncation, also known as delayed entry, is the phenomenon where certain participants enter the study after the onset of disease under study. These individuals with an event prior to their potential study entry time are not included in the analysis and this can induce selection bias. In order to address unmet needs in appropriate methods and software for competing risks data analysis, this thesis focuses the following development of application and methods. First, we develop a convenient and exible tool, the R package intccr, that performs semiparametric regression analysis on the CIF for interval-censored competing risks data. Second, we adopt the augmented inverse probability weighting method to deal with both interval censoring and missing event types. We show that the resulting estimates are consistent and double robust. We illustrate this method using data from the East-African International Epidemiology Databases to Evaluate AIDS (IeDEA EA) where a significant portion of the event types is missing. Last, we develop an estimation method for semiparametric analysis on the CIF for competing risks data subject to both interval censoring and left truncation. This method is applied to the Indianapolis-Ibadan Dementia Project to identify prognostic factors of dementia in elder adults. Overall, the methods developed here are incorporated in the R package intccr. / 2021-05-06