Feasibility of investigating methylphenidate for the treatment of sarcoidosis-associated fatigue (the FaST-MP study): a double-blind, parallel-arm randomised feasibility trial.

INTRODUCTION: Sarcoidosis-associated fatigue (SAF) is a common clinical problem with limited treatment options. This study was undertaken to determine the feasibility of performing a definitive trial to determine the clinical efficacy methylphenidate in SAF. METHODS: This was a parallel-arm, double-blind, placebo-controlled randomised controlled feasibility trial enrolling sarcoidosis patients reporting significant fatigue. Patients with a Fatigue Assessment Scale score of more than 21 were randomised to receive up to either 10 mg two times per day methylphenidate or identical placebo capsules two times per day, in a dose escalation fashion, for up to 24 weeks. Outcomes included number of participants eligible and willing to participate, withdrawal rates, adherence rates and ability to maintain blinding. RESULTS: Of 385 patients screened, 56 (14.5%) were eligible and 23 (41% of eligible patients) were randomised. No withdrawals occurred. One participant in the methylphenidate arm discontinued study medications due to chest pain. The side effect profile was not different between the groups. Median medication adherence rates were 98% and 99% in the methylphenidate and placebo arms, respectively. A greater proportion of participants receiving methylphenidate predicted their allocated treatment while blinded compared with those receiving placebo (93.3% vs 57.1%). The investigator could not predict the treatment allocation. Both groups showed clinically meaningful improvements in fatigue from baseline, although no between-group difference was seen. CONCLUSIONS: The data support the feasibility of performing a double-blind parallel trial powered to determine the clinical efficacy of methylphenidate for SAF, however, a multicentre study will be required. TRIAL REGISTRATION NUMBER: NCT02643732.

Women's perceptions of COVID-19 and their healthcare experiences: a qualitative thematic analysis of a national survey of pregnant women in the United Kingdom.

BACKGROUND: The aim of this national survey was to explore pregnant women's perceptions of COVID-19 and their healthcare experiences. METHODS: Through patient and public involvement, a questionnaire was developed and advertised via the BBC website, Twitter and other online media during May 2020. The findings were analysed by qualitative thematic analysis. Women who are currently pregnant, or who have delivered during the COVID-19 pandemic were invited to partake in a national online survey. RESULTS: One thousand four hundred fifty-one participants replied to the online questionnaire. Participants provided significant insight into the perceived barriers to seeking healthcare during this pandemic. These include 'not wanting to bother anyone', 'lack of wider support from allied healthcare workers' and the influence of the media. Other concerns included the use of virtual clinics antenatally and their acceptability to patients, the presence of birthing partners, and the way in which information is communicated about rapidly changing and evolving services. The influence of the media has also had a significant impact on the way women perceive hospital care in light of COVID-19 and for some, this has shaped whether they would seek help. CONCLUSIONS: This is the first ever reported study in the United Kingdom to explore pregnant women's perceptions of COVID-19 and their subsequent healthcare experiences. It has also provided insight into perceived barriers into seeking care as well as maternal concerns antenatally, intrapartum and postpartum.

Performance management: a qualitative study of relational boundaries in personal assistance.

Personal assistance (PA) is a model of support where disabled people take control of recruiting, training and managing the people that support them. Personal assistance differs from other forms of care, such as domiciliary or informal care, because the disabled person is in control of how, when and by whom they are supported. With the advent of personal health budgets, PA is no longer limited to social care but is also central to future NHS services and funding arrangements. The aims of this study were to gain a deeper understanding of PA relationships, and to explore how both parties manage interpersonal challenges. We report on data from 58 qualitative interviews with disabled employers and personal assistants. Applying concepts from Goffman's (1959) scheme of impression management, we present an analysis of the relational dynamics that occur when two people cooperate in shared endeavours. Goffman's concepts of team members and non-persons, in addition to the themes of regions and information control, aid a more fundamental understanding of the relational dynamics that occur between disabled employers and their PAs.

The experiences of midwives and women during intrapartum transfer from one-to-one midwife-led birth environments to obstetric-led units.

OBJECTIVE: To explore the transition from midwifery one-to-one support in labour within a midwife-led birth environment to an obstetric-led unit from the perspectives of midwives and women. DESIGN: Ethnographic study. Data was collected from eleven transfers to an obstetric-led unit. The transfer process was observed for four women. Semi-structured interviews were completed following the births with eleven women and eleven midwives. Nine maternity records were also analysed. SETTING: An alongside midwife-led unit, freestanding midwife-led unit, women's homes in England. FINDINGS: Territorial behaviour was the main theme experienced by midwives when transferring women to obstetric-led units. Territorial behaviour manifested itself as a feeling of 'us versus them' behaviours, 'feeling under scrutiny' and being aware of 'conflicting ideologies'. For women there were four themes that had an impact on their experiences of transfer obstetric-led units including: (1) their midwife continuing the care on the labour ward, (2) having time to adjust to their new situation, (3) all staff introducing themselves and (4) not being separated from their baby for long periods of time. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Transfer from a midwife-led birth environment to an obstetric-led unit is a stressful situation for midwives and women. This paper highlights how territorial behaviours impacted negatively for midwives during transfer to an obstetric-led unit. More research is required to understand territorial behaviours within the maternity services and how more respectful compassionate working relationships can be created. Additionally, from the perspective of women this paper highlights four aspects of care that positively impacted on the experiences of women and even helped them to build resilience to cope with the change of location, situation, medical interventions and new carers when transferring to an obstetric-led unit.

Midwifery one-to-one support in labour: More than a ratio.

OBJECTIVE: To explore midwifery one-to-one support in labour in a real world context of midwife-led birth environments. DESIGN: Ethnographic study. Data was collected from 30 observations inside and outside the birth environments in three different birth settings. Semi-structured interviews were completed following the births with 29 low-risk women and 30 midwives with at least one year labour support experience to gain their perspectives. Twenty-seven maternity records were also analysed. SETTING: An alongside midwife-led unit, freestanding midwife-led unit and women's homes in England. FINDINGS: Six components of care were identified that required balance inside midwife-led birth environments: (1) presence, (2) midwife-woman relationships, (3) coping strategies, (4) labour progress, (5) birthing partners and (6) midwifery support. Midwives used their knowledge, experience and intuitive skills to synchronise their care for the six components to work in balance. Balancing of the six components have been translated into continuums representing the labour care and requirements. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Midwifery one-to-one support in labour is more than a ratio when translated into clinical practice. When the balance of the six components were tuned into the needs of women, women were satisfied with their labour and birth experience, even when it did not go to plan. A one midwife to one woman ratio should be available for all women in labour.

Making sense of concept analysis.

BACKGROUND: Concept analysis is frequently the first step novice nurse researchers take when beginning their work. However, the value of concept analysis in generating theory is debated, and although there are many models researchers can use, few provide guidance for applying them or overviews of their philosophical underpinnings. AIM: To share learning about challenges encountered when undertaking concept analysis and to present an adaptation of Rodgers ( 1989 ) model created to overcome these. DISCUSSION: The authors explore the philosophical underpinning of several models of concept analysis and present an adapted model based on the work of Rogers ( 1989 ) and Tofthagen and Fagerstrøm ( 2010 ). CONCLUSION: Concept analysis is a valuable tool when used with an understanding of a model's philosophical underpinnings and sufficient measures are taken to assure analytical depth, rigour and transparency. IMPLICATIONS FOR PRACTICE: The experiences of a novice nurse researcher described in this paper will be helpful in informing others who are starting a study.

Near-infrared spectroscopy (NIRS) for a real time monitoring of the biogas process.

In this research project Near-infrared spectroscopy (NIRS) was applied to monitor the content of specific process parameters in anaerobic digestion. A laboratory scaled biogas digester was constantly fed every four hours with maize- and grass silage to keep a base load with an organic loading rate (OLR) of 2.5 kg oDM/m3 ∗ d. Daily impact loads with shredded wheat up to an OLR of 8 kg oDM/m3 ∗ d were added in order to generate peaks at the parameters tested. The developed calibration models are capable to show changes in process parameters like volatile fatty acids (VFA), propionic acid, total inorganic carbon (TIC) and the ratio of the volatile fatty acids to the carbonate buffer (VFA/TIC). Based on the calibration of the models for VFA and TIC, the values could be predicted with an R2 of 0.94 and 0.97, respectively. Moreover, the residual prediction deviations were 4.0 and 6.0 for VFA and TIC, respectively.

Feasibility study of a randomised controlled trial to investigate the treatment of sarcoidosis-associated fatigue with methylphenidate (FaST-MP): a study protocol.

INTRODUCTION: Fatigue is a frequent and troublesome manifestation of chronic sarcoidosis. This symptom can be debilitating and difficult to treat, with poor response to the treatment. Symptomatic management with neurostimulants, such as methylphenidate, is a possible treatment option. The use of such treatment strategies is not without precedent and has been trialled in cancer-related fatigue. Their use in sarcoidosis requires further evaluation before it can be recommended for clinical practice. METHODS AND ANALYSIS: The Fatigue and Sarcoidosis-Treatment with Methylphenidate study is a randomised, controlled, parallel-arm and feasibility trial of methylphenidate for the treatment of sarcoidosis-associated fatigue. Patients are eligible if they have a diagnosis of sarcoidosis, significant fatigue (measured using the Fatigue Assessment Scale) and have stable disease. Up to 30 participants will be randomly assigned to either methylphenidate (20 mg two times per day) or identical placebo in a 3:2 ratio for 24 weeks. The primary objective is to collect data determining the feasibility of a future study powered to determine the clinical efficacy of methylphenidate for sarcoidosis-associated fatigue. The trial is presently open and will continue until July 2018. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the Cambridge Central Research Ethics Committee on 21 June 2016 (reference 16/EE/0087) and was approved and sponsored by the Norfolk and Norwich University Hospital (reference 190280). Clinical Trial Authorisation (EudraCT number 2016-000342-60) from the Medicines and Healthcare products Regulatory Agency (MHRA) was granted on 19 April 2016. Results will be presented at relevant conferences and submitted to appropriate journals following trial closure and analysis. TRIAL REGISTRATION NUMBER: NCT02643732; Pre-results.

A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.

High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n = 13,781). We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region). Seven SNPs showed a genome-wide significant association with coronary artery disease (CAD) risk. A rare SNP (rs186696265; MAF ∼1%) showed the highest effect on Lp(a) and was also associated with increased risk of CAD (odds ratio = 1.73, P = 3.35 × 10-30). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number of Lp(a)-increasing alleles. We found the APOE2-determining allele of rs7412 to be significantly associated with Lp(a) concentrations (P = 3.47 × 10-10). Each APOE2 allele decreased Lp(a) by 3.34 mg/dl corresponding to ∼15% of the population's mean values. Performing a gene-based test of association, including suspected Lp(a) receptors and regulators, resulted in one significant association of the TLR2 gene with Lp(a) (P = 3.4 × 10-4). In summary, we identified a large number of independent SNPs in the LPA gene region, as well as the APOE2 allele, to be significantly associated with Lp(a) concentrations.

[Usage patterns of internet and computer games : Results of an observational study of Tyrolean adolescents]. / Nutzungsmuster von Internet und Computerspielen : Ergebnisse einer Beobachtungsstudie an Tiroler Jugendlichen.

BACKGROUND: The use of digital media such as the Internet and Computer games has greatly increased. In the western world, almost all young people regularly use these relevant technologies. Against this background, forms of use with possible negative consequences for young people have been recognized and scientifically examined. The aim of our study was therefore to investigate the prevalence of pathological use of these technologies in a sample of young Tyrolean people. METHODS: 398 students (average age 15.2 years, SD ± 2.3 years, 34.2% female) were interviewed by means of the structured questionnaires CIUS (Internet), CSV-S (Computer games) and SWE (Self efficacy). Additionally, socio demographic data were collected. RESULTS: In line with previous studies, 7.7% of the adolescents of our sample showed criteria for problematic internet use, 3.3% for pathological internet use. 5.4% of the sample reported pathological computer game usage. The most important aspect to influence our results was the gender of the subjects. Intensive users in the field of Internet and Computer games were more often young men, young women, however, showed significantly less signs of pathological computer game use. CONCLUSIONS: A significant percentage of Tyrolean adolescents showed difficulties in the development of competent media use, indicating the growing significance of prevention measures such as media education. In a follow-up project, a sample of adolescents with mental disorders will be examined concerning their media use and be compared with our school-sample.

A genome-wide association meta-analysis on apolipoprotein A-IV concentrations.

Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 - 44), rs5104 in APOA4 (P = 1.79 × 10-24) and rs4241819 in KLKB1 (P = 5.6 × 10-14). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 - 07). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10-05). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1 The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations.

Hymen reconstruction as pragmatic empowerment? Results of a qualitative study from Tunisia.

Hymen reconstruction surgery (HR), while ethically controversial, is now available in many countries. Little clinical evidence and hardly any surgical standards support the intervention. Nearly as scarce is social science research exploring women's motivations for the intervention, and health care professionals' justifications for its provision. In order to better understand decision-making processes, we conducted semi-structured interviews in metropolitan Tunis, in 2009, with six women seeking the procedure, four friends who supported such women, four physicians who perform the operation, and one midwife. Health care professionals and patient companions expressed moral ambivalence about HR: although they could comprehend the individual situation of the women, they expressed concern that availability of the procedure might further entrench the patriarchal norms that compel the motivation for seeking HR in the first place. Some women seeking HR shared this concern, but felt it was not outweighed by their personal aims, which were to marry and become mothers, or to overcome past violent sexual experiences. The women felt HR to be uniquely helpful in achieving these aims; all made pragmatic decisions about their bodies in a social environment dominated by patriarchal norms. The link between HR and pervasive gender injustice, including the credible threat of serious social and physical harm to women perceived to have failed to uphold the norm of virginity before marriage, raises questions about health care professionals' responsibility while facing requests for HR. Meaningful regulatory guidance must acknowledge that these genuine harms are at stake; it must do so, however, without resorting to moral double standards. We recommend a reframing of HR as a temporary resource for some women making pragmatic choices in a context of structural gender injustice. We reconfirm the importance of factual sexual and reproductive education, most importantly to counter distorted beliefs that conflate an "intact hymen" with virginity.

Validation of Next-Generation Sequencing of Entire Mitochondrial Genomes and the Diversity of Mitochondrial DNA Mutations in Oral Squamous Cell Carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is mainly caused by smoking and alcohol abuse and shows a five-year survival rate of ~50%. We aimed to explore the variation of somatic mitochondrial DNA (mtDNA) mutations in primary oral tumors, recurrences and metastases. METHODS: We performed an in-depth validation of mtDNA next-generation sequencing (NGS) on an Illumina HiSeq 2500 platform for its application to cancer tissues, with the goal to detect low-level heteroplasmies and to avoid artifacts. Therefore we genotyped the mitochondrial genome (16.6 kb) from 85 tissue samples (tumors, recurrences, resection edges, metastases and blood) collected from 28 prospectively recruited OSCC patients applying both Sanger sequencing and high-coverage NGS (~35,000 reads per base). RESULTS: We observed a strong correlation between Sanger sequencing and NGS in estimating the mixture ratio of heteroplasmies (r = 0.99; p<0.001). Non-synonymous heteroplasmic variants were enriched among cancerous tissues. The proportions of somatic and inherited variants in a given gene region were strongly correlated (r = 0.85; p<0.001). Half of the patients shared mutations between benign and cancerous tissue samples. Low level heteroplasmies (<10%) were more frequent in benign samples compared to tumor samples, where heteroplasmies >10% were predominant. Four out of six patients who developed a local tumor recurrence showed mutations in the recurrence that had also been observed in the primary tumor. Three out of five patients, who had tumor metastases in the lymph nodes of their necks, shared mtDNA mutations between primary tumors and lymph node metastases. The percentage of mutation heteroplasmy increased from the primary tumor to lymph node metastases. CONCLUSIONS: We conclude that Sanger sequencing is valid for heteroplasmy quantification for heteroplasmies ≥10% and that NGS is capable of reliably detecting and quantifying heteroplasmies down to the 1%-level. The finding of shared mutations between primary tumors, recurrences and metastasis indicates a clonal origin of malignant cells in oral cancer.

Lipoprotein (a) concentrations, apolipoprotein (a) phenotypes, and peripheral arterial disease in three independent cohorts.

AIMS: The relevance of lipoprotein(a) [Lp(a)] concentrations and low-molecular-weight (LMW) apo(a) phenotypes in peripheral arterial disease (PAD) has only been investigated by few studies. Therefore, we analysed this association in three independent cohorts and performed a Mendelian Randomization approach using instrumental variable regression. METHODS AND RESULTS: Lp(a) concentrations, apo(a) phenotypes, and one SNP in the LPA gene (rs10455872) were measured in the CAVASIC study, including 241 male patients with intermittent claudication and 246 age- and diabetes-matched controls as well as in the two population-based studies KORA F3 (n = 3184) and KORA F4 (n = 3080). In KORA F3/F4, 109/80 persons suffered from intermittent claudication, 200/144 from PAD, and 128/103 showed an ankle-brachial index (ABI) <0.9. In CAVASIC, adjusted logistic regression analyses revealed significant associations between an increase of log-Lp(a) per one standard deviation (SD) (OR = 1.28, P = 0.02) as well as LMW apo(a) phenotypes and symptomatic PAD (OR = 1.65, P = 0.03). Linear regression models with continuous ABI showed a significant association in the combined analyses of KORA F3/F4: an increase in log-Lp(a) per one SD (ß = -0.006, P = 0.005) and the presence of LMW apo(a) phenotypes (ß = -0.011, P = 0.02) or the minor allele of rs10455872 (ß = -0.016, P = 0.03) were associated with a decrease in ABI in the fully adjusted linear and instrumental variable regression models. CONCLUSION: Analyses in three independent populations showed significant associations of Lp(a) concentrations, LMW apo(a) phenotypes, and rs10455872 with PAD. This points to a causal relationship between Lp(a) and PAD since the genetically determined apo(a) phenotypes and SNP alleles are indeed associated with PAD.

Towards an understanding of resilience and its relevance to medical training.

OBJECTIVES: This article explores the concept of resilience and its potential relevance to medicine. It also looks at the dimensions of resilience and its ethical importance for effective professional practice, and considers whether a focus on resilience might be useful in medical training. METHODS: An applied literature search was conducted across the domains of education, ethics, psychology and sociology to answer the research question: 'What is resilience and what might it mean for professional development in medical education?' This article predominantly considers the findings in relation to training in undergraduate and postgraduate settings, although the literature is wide-ranging and findings may be applicable elsewhere. RESULTS: Resilience is a dynamic capability which can allow people to thrive on challenges given appropriate social and personal contexts. The dimensions of resilience (which include self-efficacy, self-control, ability to engage support and help, learning from difficulties, and persistence despite blocks to progress) are all recognised as qualities that are important in clinical leaders. Much of what is deemed good practice in modern pedagogical approaches to medical training may support the development of resilience in adulthood, but this concept has rarely been used as a goal of professional development. More research is needed on the ways in which resilience can be recognised, developed and supported during and after clinical training. CONCLUSIONS: Resilience is a useful and interesting construct which should be further explored in medical education practice and research.

The limits of empathy: problems in medical education and practice.

Empathy is commonly regarded as an essential attribute for doctors and there is a conviction that empathy must be taught to medical students. Yet it is not clear exactly what empathy is, from a philosophical or sociological point of view, or whether it can be taught. The meaning, role and relevance of empathy in medical education have tended to be unquestioningly assumed; there is a need to examine and contextualise these assumptions. This paper opens up that debate, arguing that 'empathy', as it is commonly understood, is neither necessary nor sufficient to guarantee good medical or ethical practice.

Qi Gong exercises and Feldenkrais method from the perspective of Gestalt concept and humanistic psychology.

This study describes two similar approaches to human movement: Qi Gong exercises and the Feldenkrais method. These systems are investigated in terms of Gestalt concepts and humanistic psychology. Moshe Feldenkrais created the concept known as Awareness Through Movement. This concept assumes that by becoming more aware of one's movements, one functions at a higher level. In similar ways to those using the Feldenkrais method, individuals may become more aware of their own movements by performing Qi Gong exercises: A therapeutic modality that facilitates mind-body integration. Qi Gong exercises commonly lead to increased personal awareness accompained by enhanced quality, fluency and smoothness of movement. These two methods of movement therapies are explored in terms of their relations with Gestalt concept and humanistic psychology.

A mixed-method approach to sense of coherence, health behaviors, self-efficacy and optimism: towards the operationalization of positive health attitudes.

This study discusses the results of a cross-sectional survey of healthy college students in Poland. More specifically, it describes, explores, and explains the relationships between psychological variables/models such as health behaviors (HB), sense of coherence (SOC), level of optimism (LOO), and self-efficacy (SE) among college students. These separate constructs have also been used to operationalize a positive health attitude (PHA) as a novel construct. The social survey was carried out at three higher education institutions in Poland in January 2006. The random sample of 455 undergraduate students was taken from five different faculties: Physiotherapy, Physical Education, Tourism and Recreation, English Philology and Polish Philology. Four reliable and validated research tools were used to collect the data: Juczynsky's Health Behaviour Inventory (HBI); Antonovsky's Sense of Coherence Questionnaire (SOC-29); Schwarzer & Jerusalem's Generalized Self-Efficacy Scale (GSES); and Seligman's Scale (SS). The results indicate statistically significant differences (p < 0.001) between these four variables: for example, the healthier health behaviors the stronger the sense of coherence, level of optimism and self-efficacy. It was also demonstrated that LOO, SOC, SE, and HB correlate with one another. Finally, these variables create an explicit empirical-theoretical pattern. All the research results from REGWQ tests, Pearson's correlation coefficient and cluster analysis suggest the existence of conceptual similarities between these four variables and/or the existence of some broader scientific construct such as PHA. However, this needs to be examined further. These results could be a good indicator for future research among different faculties or age groups.

Complex syndromes, ambivalent diagnosis, and existential uncertainty: the case of Systemic Lupus Erythematosus (SLE).

Systemic Lupus Erythematosus (SLE), also known as lupus, is an autoimmune disorder which is difficult to diagnose due to its manifold symptoms. Its complexity is part and parcel of the epistemological changes that scientific biomedicine is undergoing which in turn influence clinical practice. These changes lead to the well known and often-discussed frustration of patients who suffer from elusive disorders, long-term or chronic illnesses, and medically unexplained symptoms. Using ethnographic observations in combination with grounded theory methods this study explores SLE as one example of complex syndromes that the clinical practice of late modernity seems to bring about. It concentrates on the difficulties of diagnosing complex disorders from a medical point of view, then goes on to describe the impact this has on patients' lives, and their reaction to this situation. I argue that ambivalent diagnosis leads to existential uncertainty amongst patients which in turn influence the doctor-patient relationship. In concluding, I suggest that medical sociology has to move from merely describing and analysing this emerging situation to suggesting strategies for integrating experiential knowledge into clinical practice, especially when it comes to medical and personal management of chronic disorders such as SLE.