High tumor mutation burden predicts favorable outcome among patients with aggressive histological subtypes of lung adenocarcinoma : A population-based single-institution study

Objectives: Tumor mutation burden (TMB) is an emerging predictive cancer biomarker. Few studies have addressed the prognostic role of TMB in non-small cell lung carcinoma, with conflicting results. Moreover, the association of TMB with different histological subtypes of lung adenocarcinoma has hitherto not been systematically evaluated. Here we studied the prognostic value of TMB and its distribution in different histological subtypes of lung adenocarcinomas in a retrospective cohort using the most recent updated classification guidelines. Materials and methods: 176 surgically resected stage I-IV lung adenocarcinomas were histologically reclassified according to WHO 2015 guidelines. A modified classification subdividing the acinar subtype into classic acinar, complex glandular and cribriform subtypes was further applied and potentially prognostic histopathological characteristics such as tumor-infiltrating lymphocytes were evaluated. 148 patients with stage I-III tumors and complete follow-up data were included in the survival analyses. TMB was determined by a commercial next generation sequencing panel from 131 tumors, out of which 105 had survival data available. Results: Predominant micropapillary, solid and complex glandular as well as nonpredominant cribriform histological subtypes were associated with significantly shorter survival. High TMB concentrated in micropapillary, solid and acinar predominant subtypes. Interestingly, TMB >= 14 mutations/MB conferred a stage- and histology-independent survival benefit compared to TMB <14 in multivariable analysis for overall (HR 0.284, 95% CI 0.14-0.59, P=0.001) and disease-specific survival (HR 0.213, 95% CI 0.08-0.56, P=0.002). Conclusion: TMB was an independent biomarker of favorable prognosis in our cohort of lung adenocarcinoma despite being associated with predominant histological subtypes considered aggressive.Peer reviewe

Comprehensive genomic profiling of Finnish lung adenocarcinoma cohort reveals high clinical actionability and SMARCA4 altered tumors with variable histology and poor prognosis

Introduction: Lung adenocarcinoma is the most common type of lung cancer and typically carries a high number of mutations. However, the genetic background of the tumors varies according to patients' ethnic background and smoking status. Little data is available on the mutational landscape and the frequency of actionable genomic alterations in lung adenocarcinoma in the Finnish population. Materials and methods: We evaluated the gene alteration frequencies of 135 stage I-IV lung adenocarcinomas operated at Turku University Hospital between 2004 and 2017 with a large commercial comprehensive genomic profiling panel. Additionally, we correlated the alterations in selected genes with disease outcomes in 115 stage I-III patients with comprehensive follow-up data. The genomic alterations in a sub-cohort of 30 never-smokers were assessed separately. Results: Seventy percent of patients in the overall cohort and 77% in the never-smoker sub-cohort harbored an alteration or a genomic signature targetable by FDA and/or EMA approved drug for non-small cell carcinoma, respectively. In multivariable analysis for disease-specific survival, any alteration in SMARCA4 (DSS; HR 3.911, 95%CI 1.561-9.795, P = 0.004) exhibited independent prognostic significance along with stage, tumor mutation burden, and predominant histological subtypes. Conclusions: Over two thirds of our overall cohort, and especially never-smokers had an actionable genomic alteration or signature. SMARCA4 alterations, detected in 7.4% of the tumors, independently predicted a shortened overall and disease-specific survival regardless of the alteration type. Most SMARCA4 alterations in our cohort were missense mutations associated with differentiated predominant histological subtypes and immunohistochemical SMARCA4/BRG1 and TTF-1 positive status.</p

Caring needs in patient-partner dyads affected by heart failure : An evaluation of the long-term effects of a dyadic psycho-educational intervention

Introduction: As medical treatment has improved, patients with heart failure (HF) now live longer and care mostly takes place at home with partners providing the main assistance. Taking care of an ill or disabled individual imposes a well-documented burden on the partner’s healthrelated quality of life. The awareness of partners’ burdensome situation is increasing, but few interventions have targeted the needs of patientpartner dyads with HF. The results have been inconclusive and give no clear guidance on how interventional programmes should be designed to improve both patient and partner outcomes. Aim: The overall aim of this thesis was to evaluate the effects of a psychoeducational intervention delivered to patient-partner dyads with HF during long-term follow-up, and to explore the dyads’ perceived caring needs. Methods: The thesis is based on four papers that used both quantitative and qualitative data. Study I and II used a randomized controlled design with a follow-up assessment after 24 months including 155 patientpartner dyads. The control group received care as usual. The intervention group received care as usual, and in addition they participated in the nurse-led psycho-educational intervention. Data was collected using questionnaires before and 24 months after the intervention, in order to determine the long-term effects on patients and partners regarding health related quality of life, perceived control, symptoms of depression and partners’ caregiver burden (I, II). A conceptual health promotion model inspired the intervention. To describe how the model was applied, a qualitative approach analysing nurses’ documentation of the sessions with 71 dyads in the intervention group (III) was used. Study IV has an explorative design. To further explore the dyads’ perceived caring needs, focus groups interviews with 19 patient-partner dyads with heart failure (IV) were performed. Results: The intervention did not have any significant effect on physical or mental health- related quality of life, depressive symptoms, or perceived control over the heart failure among the dyads (I) or caregiver burden in the partners (II) after 24 months. Furthermore, time to first event did not differ significantly between the dyads in the intervention group and the control group (I, II). As for the partners, both the intervention and control group reported decreased physical health between the baseline assessment and the 24-month follow-up (I). The intervention was composed of three components; 1) cognitive 2) supportive, and 3) behavioural component. The analysis of the nurses’ documentation confirmed the coverage of all the components and the analysis revealed a vide range of caring needs among the dyads (III). The dyads described a need to learn about HF to be able to manage everyday life. Regular outpatient clinic visits and access to telephone support were vital and both the patient and the partner need to be present at the clinic visits. Meeting others who are in the same situation and sharing the burden in nurse-led group sessions was proposed as an opportunity to support each other and others (IV). Conclusions: Over the 24-month follow-up period, the intervention had a neutral effect on health- related quality of life, depressive symptoms and perceived control over the HF among the dyads, and on partners’ caregiver burden. Considering the fact that partners serve as a critical extension of the formal healthcare system, and that both patients and partners ask for more support, it will become crucial to find new ways to support dyads affected by heart failure. This thesis may be viewed as a first step in trying to understand dyads’ perceived caring needs, and it can serve as a guide in clinical work and when designing new dyadic interventions

Samtal om hjärtat : Det vårdande samtalet och dess innebörd för patienter drabbade av hjärtinfarkt.

Att ena dagen vara frisk och mitt i livet och nästa dag drabbas av akut och allvarlig sjukdom leder för patienten till en känsla av kaos. Under vårdtiden ska sjuksköterskan hjälpa patienten genom detta kaos och förbereda patienten för att lämna sjukhuset och fortsätta med sitt liv. Detta görs genom vårdande samtal som syftar till att informera om sjukdomen, riskfaktorer och livsstilsförändringar. Samtalen har också en stödjande funktion. Syftet med examensarbetet är att utifrån hjärtinfarktpatienters upplevelser beskriva innebörden av det vårdande samtalet med sjuksköterskan. Det teoretiska perspektivet är det vårdande samtalet. Data utgörs av intervjuer med tio hjärtinfarktpatienter cirka två veckor efter utskrivningen. Lindseth och Norbergs (2004) fenomenologiska hermeneutiska metod användes vid analysen av berättelserna. Resultatet visar att samtalen innebär en möjlighet för patienten att få kunskap om sjukdomen men för att samtalet ska hjälpa patienten vidare kan det inte standardiseras utan det måste fördjupas. Patienten måste få känna att sjuksköterskan har tid att lyssna och vara närvarande för att delaktighet ska uppnås. Först då kan samtalet djupna och få den vårdande innebörd som är så viktig för patienten.That one day be healthy and in the middle of the life and the next day suffering from acute and severe illness leads for the patient to a sense of chaos. During the time at the hospital the nurse will help the patient through this chaos and prepare the patient to leave hospital and get on with his life. This is done through caring conversation, which aims to provide information on the disease, risk factors and lifestyle changes. The caring conversations also have a supporting role. The aim of the study is to, on the basis of the heart infarction patient’s perspective, describe the meaning of nurse’s conversation. The frame is the caring conversation. Data consists of interviews with ten heart infarction-patients two weeks after discharge from the hospital. The methodological approach was phenomenological- hermeneutic as described by Lindseth and Norberg (2004). The result showed that the conversation means an opportunity for the patient to get knowledge about the disease, but the conversation can not be standardized if the patient should get help to get on with his life. The patient must feel that the nurse have time to listen, being present and involve the patient in the conversation. At that time, and not before that, the conversation turns to the caring conversation that means so much for the patient’s recovery

File S2. Study protocol translation in English.

<p>Study protocol translation in English.</p

Implementation of Telemonitoring in Health Care : Facilitators and Barriers for Using eHealth for Older Adults with Chronic Conditions

PURPOSE: The retrospective study used a hybrid design aimed to a) describe the implementation process of telemonitoring from stakeholders' perspectives and b) identify facilitators and barriers perceived by the care team. PATIENTS AND METHODS: Qualitative interview data were analyzed using manifest inductive qualitative content analysis to describe what was perceived as barriers and what facilitated the implementation. Participating healthcare professionals recruited from a multi-professional care team in Sweden. Overall, 14 healthcare professionals comprising 8 assistant nurses, 3 nurses, 1 physiotherapist, 1 occupational therapist, and one general practitioner participated in five interviews. RESULTS: Four categories were derived from the interview analysis: previous experience with digital technology, the need for preparation before implementation, perceptions of using telemonitoring in daily practice from the patient's perspective, and perceptions of the relevance and reasons for applying telemonitoring from the care team's perspective. The identification of stakeholders and the need to plan carefully when proposing the introduction of telemonitoring systems into work practices are both crucial. CONCLUSION: The attitudes of healthcare professionals can be a significant factor in the acceptance and efficiency of the use of telemonitoring in practice. Therefore, implementing new technology in healthcare should involve healthcare professionals at an early stage to gain common understanding

Introducing nurse-led heart failure clinics in Swedish primary care settings

AIM: According to clinical guidelines, it is recommended that patients with heart failure (HF) receive structured multidisciplinary care at nurse-led HF clinics in order to optimise treatment and avoid preventable readmissions. Today, there are HF clinics with specialist-trained nurses at almost all Swedish hospitals, but HF clinics remain scarce in primary care (PC). The aim of this study was two-fold: firstly, to evaluate the effects of systematically implementing nurse-led HF clinics in PC settings with regard to hospital healthcare utilisation and evidence-based HF treatment, and secondly to explore patients' experiences of HF clinics in PC. METHODS AND RESULTS: The study had a pre-post design. Annual measurement were done between 2010-2017 regarding in-hospital healthcare consumption and medical treatment. Data from 2011-2017 after the implementation of HF clinics in PC in one county council Sweden were compared with baseline data collected before the implementation in 2010. The implementation of HF clinics in PC significantly reduced the number of HF-related hospital admissions by 27% (P &lt; 0.001), HF hospital days by 27.3% (P &lt; 0.001) and HF emergency room visits by 24% (P &lt; 0.001). Further, patients were to a higher extent medically treated according to guidelines and satisfied with the care they received at the PC HF clinic. CONCLUSION: Nurse-led HF clinics in PC seem to be effective in reducing the need for in-hospital care and provide high quality person-centred care

Raw data Table 4. Multiple linear regression analyses (robust variance estimates) to detect intervention effects regarding health, symptoms of depression and perceived control for both patients and partners

<p>Raw data Table 4. Multiple linear regression analyses</p

The systematic work environment management on the building site

Syfte: Byggbranschen är den verksamhets som drabbas utav mest arbetsolyckor och arbetsskador och detta kan vara ett resultat utav bristande arbetsmiljöarbete. JM Entreprenad är ett bygg- och anläggningsentreprenad där arbetsmiljön är en högt prioriterad fråga. Trots detta sker det arbetsolyckor och brister i arbetsmiljöarbetet. Denna rapport kommer därför att undersöka företagets systematiska arbetsmiljöarbete och komma med förslag till ett förbättrat arbetsmiljöarbete. Metod: För att uppnå målet med studien har en kombination av kvalitativa och kvantitativa metoder använts. Information samlades delvis in i form av en enkät bestående av 15 anonyma respondenter som representerar JM Entreprenads yrkesarbetares upplevelser kring det systematiska arbetsmiljöarbetet på företagets byggarbetsplatser. En dokumentstudie genomfördes för att hitta en koppling mellan SAM och sänkt olycksfrekvens. Olycksstatistik från SCB och AFA-försäkring analyserades för att ta reda på anledningar till att arbetsolyckor fortfarande sker på byggarbetsplatser. Observationerna fokuserade på yrkesarbetarnas förhållningssätt till viktiga aktiviteter i det systematiska arbetsmiljöarbetet. Resultat: Systematiska arbetsmiljöarbetet är en del av det vardagliga arbetet på företaget, det finns tydliga rutiner för hur arbetet skall gå till. Enkätundersökningen visade att 100 % respondenterna är nöjda med det systematiska arbetsmiljöarbetet i dagsläget medan 6,7 % har angett att det finns brister i arbetet. Brister går att förbättra genom att bland annat förbättra kommunikationen mellan företaget och inhyrda underentreprenörer. Platsledningen bör föregå med gott omdöme för att bidra till en tillfredställande arbetsmiljö som ingår i det systematiska arbetsmiljöarbetet. Konkreta bevis och studier på huruvida införandet av det systematiska arbetsmiljöarbetet har påverkat olycksfrekvensen positivt eller negativt har inte hittats. Statistik visar att den mänskliga faktorn ofta spelar stor roll vid olyckor, därför ligger mycket av ansvaret av det systematiska arbetsmiljöarbetet på individen. Konsekvenser: Nedanstående rekommendationer sammanfattar de slutsatser som har konstaterats utifrån studien: Kommunikation om företagets arbetsmiljöarbete mellan underentreprenörer och JM Entreprenad bör förbättras. Brister i den mänskliga faktorn bör kunna reduceras genom att införa tätare pauser för att säkerställa koncentrerat arbete, att arbetsledarna inte skall låta en yrkesarbetare som är till exempel extra trött en dag arbeta med riskmoment. Skyddsronder bör inkludera fler parter. Arbetsberedningen bör involvera fler parter, detta för att alla inblandade aktörer på byggarbetsplatsen skall få en mer översikt och förståelse för arbetet runt omkring dem. Begränsningar: Denna studie har genomförts på fem byggarbetsplatser på JM Entreprenad och detta ingick i studiens avgränsning och gör undersökningen smal. För att få en mer övergripande bild av företagets arbetsmiljöarbete hade fler av företagets byggarbetsplatser kunnat undersökas. Studien är begränsad till att endast undersöka produktionen på dessa fem byggarbetsplatser

Figure 1. Flowchart for the participating dyad from enrolment until 24 months.

<p>Flowchart for the participating dyad from enrolment until 24 months.</p