Bortezomib-based induction therapies have shown to increase complete response rates and are used as an upfront therapy for newly diagnosed multiple myeloma patients. The standard treatment uses twice a week bortezomib at 1.3 mg/m^2 with dexamethasone PO on the day of and day after bortezomib, however, peripheral neuropathy is often a dose-limiting factor. For elderly patients with multiple co-morbidities and polypharmacy, we propose an alternate schedule of once a week bortezomib IV at 1.6 mg/m^2 with dexamethasone PO on the day of and day after bortezomib. In this phase II, open-labeled, multi-site study, we hypothesize that patients receiving weekly bortezomib will have comparable efficacy as the standard twice a week schedule with increased convenience and lower toxicity profile, especially related to peripheral neuropathy. METHODS: 50 patients with newly diagnosed symptomatic multiple myeloma who were ineligible for transplant or postponed transplant were enrolled from 12 Veterans Affairs hospitals. One cycle consisted of once a week 1.6 mg/m2 bortezomib IV (days 1, 8, 15, 22) plus dexamethasone PO on the day of and after bortezomib (days 1, 2, 8, 9, 15, 16, 22, 23) for 4 weeks, with the 5th week off of treatment. Responding patients could receive up to 6 cycles. RESULTS: The median age of patients was 71 ± 1.46 years (range: 50-89) with β-2 microglobulin of 5.80 ± 0.46 mg/L and c-reactive protein of 10.61 ± 5.54 mg/L. Patients also had multiple co-morbidities including cardiovascular disease (76%) renal insufficiency (54%) and pulmonary problems (36%) and were receiving a median of 13 concurrent medications at baseline. Of the fifty patients, 43 patients were evaluable for response. Seven patients received <1 cycle or died before response could be evaluated. An objective response rate of 79% was observed in 43 evaluable patients with 14% achieving nCR/CR, and at least VGPR in 44% of patients. The median progression-free survival was 9.6 months and overall survival was 46.5 months. The most common toxicity of all grades was thrombocytopenia (42%), lymphopenia (46%), asthenia (48%), and constipation (38%). Peripheral neuropathy occurred in 24% with grade 3 neuropathy occurring only in 6% of patients. In conclusion, a weekly bortezomib plus dexamethasone regimen is efficacious and safe, with lower neurotoxicity in elderly patients with newly diagnosed multiple myeloma complicated by extensive co-morbidities and polypharmacy.

Published research on diabetes in Ghana is quite limited and relates mainly to incidence and prevalence of the disease with little research on the patients experiences of coping with the diabetes. It is estimated that diabetes affects 6.3% of the Ghanaian population with type 2 diabetes accounting for 90-95% of all cases of diabetes. In Ghana, individuals diagnosed with type 2 diabetes mellitus are confronted with difficulties including the high cost of treatment of the condition, stigmatization, and interruptions to normal physiological processes. In addition, the patients experience, limited clinic accessibility, inadequate drug availability, inadequate numbers of trained staff, as well as limited availability of equipment needed for adequate care of the condition. The review of literature for this current thesis also showed that none of the studies on coping were undertaken in Ghana, but were conducted in the western world where socio-cultural factors are quite diverse from the Ghanaian situation. In the light of the challenges facing diabetic patients as well as the gap observed in literature, the study set out to explore the coping strategies of patients with type 2 diabetes mellitus at a hospital in Ghana. A hermeneutic phenomenological approach to qualitative research was utilized. Twenty seven (27) in-depth interviews carried out with newly diagnosed patients with type 2 diabetes, between August and October 2009 at a hospital in Ghana. Interviews were conducted in the local Ghanaian Twi language and English. Participants who could not speak English were interviewed in Twi language and later translated into English by the researcher. Data analysis used Creswell (1998) approach to qualitative data analysis, which provided a rich description of the essential structures of the phenomenon under study. The study identified patients’ perceptions as to the causes of diabetes mellitus, the social meanings attributed to diabetes (with particular attention paid to the language by Ghanaian people to describe disease condition), and subsequently reactions and resolutions to diagnosis. Patients discussed treatment options, while at the same time remaining hopeful of finding a cure. All patients had a firm spiritual belief system that underpinned their understanding of the causation and treatment of their illness. This combined with various degrees of understanding and acceptance of western explanations of illness influenced the coping strategies employed by patients, which variously reported as positive, negative, and alternative strategies. The study establishes a platform upon which health providers can develop educational programmes for diabetic patients in Ghana, which will address misconceptions about diabetes mellitus in Ghana and the importance of programmes of care, which take account of and build upon the cultural context of ‘being Ghanaian’. Diabetes, at least for Ghanaian patients is more than a biomedical disease. In this sense a biomedical framework in and of itself will not enable healthcare providers to effectively manage this chronic disease in the Ghanaian population, but through the inclusion of an understanding of their spiritual beliefs, healthcare providers can understand the realities of what it is like for Ghanaian diabetes patients to live with diabetes. It is argued that a stronger collaboration and integration between traditional healthcare systems and orthodox healthcare systems will provide the optimum opportunity to maximize patient care in Ghana. Future research should concentrate on better understanding how lay knowledge and health related attitudes, beliefs and behaviours are associated with diabetes in Ghana.

Background: One of nine women will at some point in life be treated for breast cancer. When a woman receives a cancer diagnosis, it can be a trigger of a life crisis, which manifests itself in different phases: shock phase, reaction phase, processing phase and reorientation phase. Breast cancer affects the women's lifeworld and create suffering. Aim: The aim of this study was to describe women's experiences of receiving a breast cancer diagnosis. Method: This is a literature-based study of twelve qualitative articles. The articles was analyzed according to a qualitative content analysis of Graneheim and Lundman (2004). Results: The findings of this study were that women with a newly-diagnosed breast cancer went through a life crisis while diagnosed. Three themes emerged; 1: 'To receive the diagnosis of breast cancer'. Subthemes that emerged in this theme was; 'To be in shock', 'Fear of the disease progress and its consequences', and 'Uncertainty about the future'. 2: 'Strategies to master the new life situation'. Subthemes was; 'Activities to manage everyday life', 'Trust in spirituality' and 'To accept the diagnosis'. 3: 'The inherent meaning of support'. Subthemes was; 'The importance of health professionals supportive and informative role' and 'The significance of family and friend's support'. Conclusion: Receiving a breast cancer diagnosis is manifested as multifaceted and had a great impact on women's lives. Spirituality had a great significance for women's life-world. How the diagnosis was received, was highly individual.

BACKGROUND: Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions of the bowel that display a rising prevalence in childhood and adolescence. The diagnosis of a chronic condition, such as IBD, in childhood can be overwhelming and stressful for both the patient and caregiver. Parents and family members can play a critical role in providing emotional support for children with newly diagnosed IBD. We hypothesized that dysfunctional patient and parental coping strategies would correlate with increased anxiety and depression in children, worsening clinical disease activity, and increased healthcare utilization. OBJECTIVE: The primary objective of the IBD Coping Study is to assess the stability of coping strategies and psychological stress over the first year following a new diagnosis of IBD. Secondarily, we aim to assess the impact of child and parental coping strategies on disease activity and emotional well-being over the year. METHODS: This is a prospective, longitudinal cohort study of children with newly diagnosed IBD and their parents at Boston Children's Hospital (BCH). Patients between the ages of 9 and 17 years old that have been diagnosed with CD, UC or Indeterminate colitis (IC) within the last 6 months, are English-speaking, and receive routine care at BCH are approached for participation in our study. Participation includes the completion of previously validated psychological metrics for both child and parent at baseline and then again 12 months later. Our instruments include the Children's Depression Inventory (CDI), the Screen for Child Anxiety Related Disorders (SCARED), the IMPACT-III Questionnaire, the Patient Health Questionnaire (PHQ-9), Healthcare Utilization Survey, Pediatric Inventory for Parents (PIP), and the Hospital Anxiety and Depression Scale (HADS). RESULTS: We screened 187 patients with IBD for participation in our study, and roughly 30% of them were eligible for recruitment. To date, we have enrolled a total of 30 patients. Of these patients, there was an equal distribution of male and female participants. The majority of patients were around 14 years of age at the time of IBD diagnosis with a greater number of patients with CD (17) currently represented. We are approaching patients on average about 1.5 months after their initial diagnosis. The baseline average Pediatric Ulcerative Colitis Activity Index (PUCAI) score was 21.15 ± 20.53, whereas the average Pediatric Crohn's Disease Activity Index (PCDAI) score was 3.75 ± 2.50. On CDI items, teenage girls and boys reported increased raw and standardized scores (Raw: 5.83 and 4.83, respectively; Standardized: 43.67 and 44.67, respectively) than their younger counterparts for depressive behaviors, including negative mood and interpersonal problems. Pediatric patients encountered as inpatients reported an overall lower quality of life on IMPACT-III items (103.29 ± 15.11) than those approached in the ambulatory setting (140.36 ± 7.50). On SCARED items, patients met criteria for the potential presence of one or more anxiety disorders. Inpatients also reported being bothered more frequently with respect to hindrances in their sleep, appetite, and daily routines on the PHQ-9 metric. Parents of children with newly diagnosed IBD rely on increased communication with their child's primary GI provider, and their scores reflected lower emotional functioning during an admission period when compared to scores reported during regular scheduled ambulatory visits. Scores collected from the HADS screen demonstrate that 6% and 33% of parents reported a score great enough to be considered a "borderline case" for depression and anxiety measures, respectively. Primary comparisons between child health assessments and parent healthcare utilization depicted concurrent elevations in the same child-parent pair at baseline. CONCLUSION: Our initial findings suggest a clear disparity between emotional stability in children and their parents in outpatient and inpatient settings following a new IBD diagnosis. Healthcare utilization by parents may be linked to adaptive or maladaptive coping, and continuation of our study will substantiate this prediction. In looking ahead, potential interventions may require approaches stratified by age, gender, and hospital setting. Our study supports the need for further investigations into the impact of targeted interventions that promote an improvement in overall quality of life in children with IBD and their family during the first year of post-diagnosis.

Bröstcancer är en av de vanligaste cancer formerna bland kvinnor runt om i världen. Beskedet bröstcancer väcker starka känslor och kan utlösa ett stort lidande. Kvinnors livsvärld förändras och livet blir centrerat kring sjukdomen. Syftet med denna studie var att beskriva kvinnors upplevelser i samband med nydiagnostiserad bröstcancer. Metoden som användes var en litteraturbaserad analys av åtta kvalitativa artiklar som analyserads och bearbetades med Evans (2003) analysmodell. Studien resulterade i tre teman: kvinnors känslor och tankar i samband med nydiagnostiserad bröstcancer; stödets betydelse för kvinnor med nydiagnostiserad bröstcancer och kvinnors upplevelse av livsförändring och framtid i samband med nydiagnostiserad bröstcancer.Resultatet visar att kvinnor som lever sina vardagliga liv går plötsligt från ett liv i säkerhet till ett liv i oro, ovisshet och förtvivlan. Därför är dessa kvinnor i stort behov av stöd efter diagnosen. Det krävs som vårdare att ha stor förståelse, öppenhet och följsamhet för att kunna möta kvinnors levda livsvärld för att kunna ge dem en bra vård, lindra lidande, främja hälsa och välbefinnande. / Program: Sjuksköterskeutbildning

Introduction: The major symptoms of fibromyalgia have been shown to severely impact everyday activities. As a consequence, many women have problems remaining in a work role. Not being able to fulfil valued roles influences quality of life. Moreover, consequences in terms of high costs in compensation for reduced work ability are also of importance for society. Today, the number of young women diagnosed with fibromyalgia is increasing. Objectives: The general aim of this thesis was to increase and deepen knowledge of the life situation of women with fibromyalgia; to examine how to manage a work role when in constant pain, and especially the situation for newly-diagnosed women. Subjects and Methods: 278 women with longstanding pain were included. The thesis includes five different studies, two of them with a focus on the work situation, two with focus on young, newly-diagnosed women’s life situation, and one investigating time-use and activity patterns in working and non-working women with fibromyalgia. Methods used are a postal questionnaire, instruments commonly used in fibromyalgia, a diary, and interviews. Results: Despite limitations in physical capacity, 48% of the women are working, full-time or part-time. However, most job loss is associated with the fibromyalgia symptoms, and the women report that the symptoms influence their daily activities during most of their waking time. There is a rapid increase in sickness absence in the newly-diagnosed women, and the young women in particular do not return to the labour market during the first year after receiving their diagnosis. The non-working women have a more demanding family situation, and are also less satisfied with their present situation than working women. Conclusion: When individual adjustments of the work situation are made and the women participate to a level that matches their ability, they are able to continue in a work role. In evaluating the women’s work capacity, the total life situation of the women should be considered. / On the day of the public defence of the doctoral thesis, the status of article III and IV was Submitted.

Background: Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease. The diagnosis is based on a combination of the motor signs: tremor, bradykinesia, rigidity and postural abnormalities. Mild Cognitive Impairment (MCI) is common early in the disease and a large proportion of patients with PD develop dementia (PDD). Associations between motor symptoms and cognitive decline have been suggested but the results are inconclusive due to differences in the selection of participants and variables tested. Large population based studies with comprehensive neuropsychological investigation in newly diagnosed cases with PD followed prospectively are rare. The aim of this thesis was to improve characterization and understanding of cognition in PD, and to explore the relationship to motor impairment in the early phase of PD. Methods: All new patients with suspected idiopathic parkinsonism in the catchment area (142 ooo inhabitants) were examined during a period of five years and four months. Among other investigations, a comprehensive neuropsychological evaluation was carried out in 119 of 148 patients with PD together with 30 age matched healthy controls. Assessments were repeated after one three and five years. Results: Patients performed worse than healthy controls in a majority of neuropsychological tests. MCI at the time of diagnosis were found in 36% according to recently published MCI criteria. Thirty % were cognitively impaired using another definition. One fourth of the patients developed PDD within five years after diagnosis and 25 % of those with MCI at baseline reversed back to normal cognition. Age and MCI were significant predictors of dementia. Education was an independent predictor for severe cognitive dysfunction at diagnosis but did not predict PDD. Patients with MCI converting to PDD had worse performance on visuospatial function, semantic fluency, episodic memory, mental flexibility and conceptual thinking. There were no differences in cognitive performance between patients with predominant Postural and Gait Disturbances (PIGD) and the tremor dominant subtype at the baseline investigation and belonging to the PIGD subgroup at baseline did not predict PDD. Dementia converters declined more rapidly than non-converters in posture/gait function. Associations between bradykinesia and measures of executive functions and working memory were found, and between posture and gait disturbances and visuospatial function. Some of these associations were persistent after one year. Patients receiving the dopamine agonist pramipexole performed significantly worse on a measure of verbal fluency at the one year follow up. Conclusions: The differences in proportions of cognitively impaired in the different studies emphasize the value of joint criteria for PD-MCI. Even when using such criteria, a substantial proportion of patients revert back to normal function. The increase in motor disability in patients with PDD could have several different causes that need to be further investigated. Associated motor and cognitive dysfunctions could reflect common pathophysiological processes in partly shared networks. Both dopaminergic and non-dopaminergic motor and cognitive functions seems to be involved in PDD which suggests that pharmacological treatment in PD needs to go beyond the scope of dopaminergic deficiency in search for new therapies that would also be effective for non-motor symptoms. / NYPUM

Bakgrund: Bröstcancer är idag den vanligaste cancerformen bland kvinnor. Att få ett besked om en livshotande sjukdom kan generera starka känslor. Hur kvinnorna hanterar ett sådant besked beror på omedvetna försvarsmekanismer och medvetna copingstrategier vilka kan vara mångfacetterade. Sjuksköterskan har en viktig roll i att stödja dessa copingstrategier för att främja en god omvårdnad.                 Syfte: Syftet var att belysa kvinnors känslor och copingstrategier efter ett bröstcancerbesked. Metod: En litteraturöversikt gjordes utifrån tolv vetenskapliga artiklar vilka analyserades enligt Fribergs metod. Artiklarna är författade mellan år 2010 och år 2018 och var av kvalitativ-, kvantitativ- och mixad metod. Utifrån artiklarnas resultat identifierades likheter och skillnader vilket resulterade i två kategorier och åtta subkategorier. Resultat: Resultat visade att vanligt förekommande känslor och copingstrategier vid ett bröstcancerbesked var olika känslor i form av chock, rädsla och ångest och oro samt copingstrategier vilka visade sig hos kvinnorna i form av förnekelse, ändra fokus, positiv attityd, social stöttning och tro. Diskussion: Diskussionen berör att ångest kan förekomma innan, under och efter att ett bröstcancerbesked givits. Ångesten är således existentiell och kan påverka livskvalitén under längre tid än vid diagnostillfället. Ändringen av fokus och prioritera saker som var betydelsefulla diskuterades ge en känsla av kontroll. Social stöttning var en copingstrategi vilken diskuterades kunna ha en positiv effekt och negativ effekt för kvinnorna. / Background: Breast cancer is the most common form of cancer among women. Receiving news regarding a life-threatening disease can cause strong emotions. How women handle such news is due to defense mechanisms and conscious coping strategies that can all be multifaceted. The nurse has an important role to support these coping strategies and to promote good caregiving. Aim: The purpose was to highlight women’s feelings and coping strategies after breast cancer diagnosis. Method: Twelve scientific articles were analyzed in the present literature review according to the method recommended by Friberg. The articles were written between year 2010 and 2018, which were of qualitative, quantitative and mixed methods. Based on the results of the articles, similarities and differences were identified which became two head categories and eight sub-categories. Results: The result showed that common kinds of feelings and coping strategies when receiving the news of breast cancer were feelings such as shock, fear and anxiety and worries. It also showed coping strategies such as denial, change of focus, positive attitude, social support and faith. Discussion: The discussion concerns that anxiety can occur before, during and after a breast cancer message. Anxiety is therefore existential and can affect quality of life for longer time than at the time of diagnosis. The change of focus and prioritizing matters that were significant were discussed to give a sense of control. Social support was a coping strategy that was discussed to have a positive and negative effect for the women.

Bakgrund: Incidensen av bröstcancer ökar i Sverige och är den vanligaste cancerformen bland kvinnor. Varje dag diagnostiseras 20 kvinnor i Sverige med bröstcancer och även om chanserna att överleva ökar, skapar denna sjukdom en stor livsomställning för de drabbade kvinnorna. Bröstcancer är en multidimensionell sjukdom vilket kan leda till att kvinnan får såväl fysiska som psykiska problem. Kvinnor som drabbas av bröstcancer genomgår en krisreaktion, som slutligen leder fram till att de får en ny syn på sitt liv och sin tillvaro. Syfte: Denna studie syftade till att beskriva kvinnors upplevelse av att leva med nydiagnostiserad bröstcancer. Metod: Detta var en empirisk studie med data insamlad från fyra bloggar skrivna av kvinnor med bröstcancer. Studiens analys genomfördes som en kvalitativ innehållsanalys och resulterade i sju områden. Resultat: De sju områdena bestod av Ångest, nedstämdhet och maktlöshet, Hopp, framtidstro och glädje i vardagen, Frustration, Förändring, Ensamhet, Förnekelse och Insikt. Detta var upplevelser som kvinnorna beskrev i sina bloggar. Slutsats: Även om en bröstcancerdiagnos innebär en stor livsomställning och att kvinnan upplever både ångest och nedstämdhet, kan de ändå uppleva en känsla av hopp och glädje inför framtiden. / Background: The incidence of breast cancer is increasing in Sweden and is the most common cancer among women. Each day, 20 women are diagnosed with breast cancer in Sweden and although the chances of survival are increasing, this disease creates a major life change for the women affected. Breast cancer is a multidimensional illness which leads to physical as well as psychological problems. Many women with breast cancer experience a life crisis which often leads to a new outlook on life and their existence. Objective: The aim of this study was to describe women’s’ experience of living with newly diagnosed breast cancer. Method: An empirical study was undertaken with data collected from four blogs. Results: The findings of this study revealed seven areas that were described in the women’s blogs. These areas were; Anxiety, depression and powerlessness, Hope, optimism and joy in everyday life, Frustration, Change, Loneliness, Denial and Personal insight. Conclusion: Women living with breast cancer do not only experience anxiety and depression, but also acknowledge a feeling a sense of joy and hope for the future as they face the challenges of this disease.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24881号 / 医博第5015号 / 新制||医||1068(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 古川 壽亮, 教授 髙橋 良輔, 教授 阪上 優 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM