Search

Background Most COVID-19 patients experience a mild course of the disease and can be managed in general practice. However, in the early pandemic, most research was conducted in secondary care. Objectives This scoping review aimed to identify original research published within the first year of the pandemic relevant to general practice regarding symptomatic, non-hospitalised patients with mild to moderate COVID-19 disease to provide an overview of published research. Methods PubMed was searched for studies written in English, Swedish, Danish, or Norwegian published before 1 April 2021. Two authors screened all titles and abstracts and identified full texts. Results We screened 1303 titles and abstracts and retrieved 128 full texts. An additional 44 full-texts were obtained from references. After full-text reading, 79 articles were included, six of which were conducted in general practice, 20 in the community, 42 in hospitals, and 11 in other settings. Therapy and harm were investigated in randomised controlled trials in 11 out of 17 studies; the diagnosis was investigated using a diagnostic accuracy design in four out of 26 studies and prognosis in prospective studies in 10 out of 21 studies. The remaining 15 studies had other research questions. Conclusion Although general practitioners in most countries must have been involved in managing patients with COVID-19, little research has been published from general practice during the first year of the pandemic. General practice research environments must be able to respond quickly in case of future pandemics.

A post-hoc exploratory analysis of the PIONEER 9 and 10 trials evaluated the effect of baseline age (

Background Immune checkpoint inhibitor (ICI)-related myocarditis is an uncommon but potentially fatal immune-related adverse event. Corticoid-resistant myocarditis induced by ICI is an important therapeutic challenge. Case summary Here, we present a case of steroid-refractory ICI-related myocarditis and myositis treated with abatacept and mycophenolate mofetil (MMF). A 57-year-old male with metastatic renal cell carcinoma was diagnosed with immune-related myocarditis and myasthenia gravis-like myositis after first dose of combination ICIs with nivolumab (anti-programmed cell death-1) plus ipilimumab (anti-cytotoxic T-lymphocyte-associated antigen-4). Twelve days after ICI he was admitted to the hospital due to palpitations, headache, and pain in the extremities. Laboratory findings revealed elevated inflammatory markers and cardiac enzymes. Electrocardiogram showed first-degree atrioventricular (AV) block and right bundle branch block which developed into complete heart block within 48 h. Because of clinical and paraclinical deterioration despite immediate initiation of methylprednisolone abatacept and MMF was added. Following, gradual subjective improvement and termination of arrhythmia led to discharge of the patient from the hospital 6 weeks after the introduction of ICI. Discussion The key treatment of ICI-related myocarditis is glucocorticoid. For steroid-refractory myocarditis supplementary immune suppressive agents are recommended. Yet, data still relies on case reports and case series, due to lack of prospective studies. In this case, the use of abatacept and MMF led to resolution of steroid-resistant ICI-related myocarditis and myositis.

Aims To assess the efficacy and safety of twice‐daily insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) twice daily, both ± metformin, in Chinese adults (N = 543) with type 2 diabetes (T2D) inadequately controlled on premixed/self‐mixed or basal insulin ± metformin. Materials and methods We conducted a 26‐week, phase III, open‐label, treat‐to‐target, 2:1 randomized trial. Hierarchical testing was used with non‐inferiority of glycated haemoglobin (HbA1c) change from baseline to week 26 as the primary endpoint and superiority for the confirmatory secondary endpoints which were as follows: change from baseline in fasting plasma glucose (FPG); nocturnal confirmed hypoglycaemic episodes (12:01–5:59 am, inclusive); total confirmed hypoglycaemic episodes (severe or plasma glucose

Introduction Knee osteoarthritis (OA) is associated with chronic knee pain and functional disability that negatively affect the ability to carry out normal daily activities. Patients are offered a large variety of non-surgical treatments, often not in accordance with clinical guidelines. This observational study will provide a comprehensive overview of treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon, including timing and order of treatment modalities, predictors of treatment outcomes, cost-effectiveness of treatment pathways and patients’ views on different treatment pathways. Methods and analysis Patients with primary referrals to an orthopaedic surgeon due to knee OA are consecutively invited to participate and fill out a questionnaire prior to their consultation with an orthopaedic surgeon. Follow-up questionnaires will be obtained at 6 and 24 months after inclusion. Based on a prospective cohort study design, including questionnaires and register data, we will (1) describe treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon; (2) describe the characteristics of patients choosing different treatment pathways; (3) develop predictive models for patient-self-determined classifications of good and poor treatment outcomes; (4) evaluate the cost-effectiveness of treatment pathways that live up to clinical guidelines versus pathways that do not; based on a qualitative study design using semistructured individual interviews, we will (5) describe the patients’ perspectives on treatment pathways for knee OA. Ethics and dissemination The study is approved by the Danish regional ethical committee (journal number H-17017295) and the Danish Data Protection Agency (journal number AHH-2017–072). Data will be anonymised and handled in line with the General Data Protection Regulation and the Danish Data Protection Act. The study results will be submitted to international open-access peer-reviewed journals and disseminated at conferences. Trial registration number NCT03746184, pre-results.

PURPOSE: To assess the association between exposure to physical workload throughout working life and risk of mobility limitations in midlife in a population-based Danish cohort.METHODS: The study was cross-sectional with a retrospective exposure assessment, and data were from a questionnaire used in the Copenhagen Aging and Biobank. Cumulative physical workload was estimated by combining information about the participants' employments and data from a job exposure matrix. Daily amount of lifting was standardised in ton-years (lifting 1000 kg/day/year) and grouped in 5 exposure groups (no/minor (1-2 ton-years)/low (3-10 ton-years)/moderate (11-20 ton-years)/high exposure (> 20 ton-years)). The outcome was self-reports of mobility limitations (running 100 m, walking 400 m, and climbing stairs to the 2nd floor) in midlife. The association between exposure and outcome was analysed using logistic regression models.RESULTS: We included 4996 men and 2247 women, mean age 56 years. 21% of men and 10% of women were in the highest exposure-group (> 20 ton-years). Higher cumulative exposure was associated with higher odds for mobility limitations. Exposure to more than 20 ton-years compared to no exposure increased the odds for limitations in walking, age-adjusted odds ratio (OR) 3.2 (95% CI: 2.4-4.3) for men, 2.3 (1.4-3.8) for women. Corresponding results for running: 2.5 (2.2-3.0) for men, 1.6 (1.2-2.2) for women, and for limitations in climbing stairs: 4.2 (3.3-5.2) for men, 1.7 (1.2-2.4) for women. Results were attenuated when confounders were added.CONCLUSIONS: Exposure to physical workload throughout working life is associated with higher odds for mobility limitations in midlife.

Aims and objectives: To investigate attitudes towards family involvement in care among a broad sample of Danish nurses from all sectors and healthcare settings. Background: Evidence suggests that nurses hold both supportive and less supportive attitudes about involvement of family members in the care of patients, and the existing findings are limited to specific healthcare contexts. Design: A cross-sectional study adhering to the Strengthening the Reporting of Observational Studies in Epidemiology for reporting observational studies. Methods: Using snowball sampling, the Families' Importance in Nursing Care-Nurses' Attitudes questionnaire was initially administered to a broad, convenience sample of Danish registered nurses through social media: Facebook interest groups and the homepage of the Danish Family Nursing Association. These nurses were encouraged to send the invitation to participate in their network of nursing colleagues. Complete data sets from 1,720 nurses were available for analysis. Results: In general, the nurses considered the family as important in patient care. Nurses who held master's and doctorate degrees scored significantly higher than nurses with a basic nursing education. Nurses who had had experience with illness within their own families tended to score higher on the family as a conversational partner subscale than those without this experience. Nurses with the longest engagement within hospital settings scored significantly lower than those with the longest engagement within primary health care and/or psychiatry. Conclusions: Families are considered important in nursing care. Younger nurses with a basic education, short-term engagement at a hospital and no experiences with illness within their own families were predictors of less supportive attitudes towards including the family in nursing care. Relevance to clinical practice: Clinical leaders and managers should promote education on the importance of active family involvement in patient care in clinical practice and undergraduate education. More focus on collaboration with families in the hospital setting is needed.

We aimed to evaluate whether macular laser still has a role in the treatment of macular oedema (MO) caused by branch retinal vein occlusion (BRVO) and provide an overview of recent studies on commonly available treatment options. A literature search was last conducted in PubMed on 26 February 2019, limited to human randomized controlled trials published in English since 2008. Seventeen articles addressing 13 trials were included in this assessment. In trials evaluating intravitreal corticosteroid and macular laser, triamcinolone was non-inferior to laser in regard to visual acuity (VA) and central retinal thickness (CRT) outcomes. Combination treatment of dexamethasone and laser resulted in better VA and lower CRT after 6 months. In trials evaluating vascular endothelial growth factor (VEGF) inhibitors versus macular laser treatment, or sham and rescue laser, better VA and CRT of VEGF inhibition treatment was consistently reported. Results of combination treatment versus VEGF inhibition monotherapy were inconsistent, with four of six studies reporting comparable outcomes and injection burden. Study comparison was affected by considerable differences in study design and inadequate reporting of laser protocol and rescue laser. Studies evaluating angiostatic treatment as monotherapy largely report the use of rescue laser, indicating that some patients would benefit from supplemental laser treatment even in the era of intravitreal therapy. Thus, we suggest further studies on optimal design of combination therapy prioritizing longer follow-up time to sufficiently evaluate the delayed effect of laser.

BACKGROUND: We aimed to investigate the effect of automated external defibrillator (AED) feedback mechanisms on survival in out-of-hospital cardiac arrest (OHCA) victims. In addition, we investigated converting rates in patients with shockable rhythms according to AED shock waveforms and energy levels.METHODS: We collected data on OHCA occurring between 2011 and 2014 in the Capital Region of Denmark where an AED was applied prior to ambulance arrival. Patient data were obtained from the Danish Cardiac Arrest Registry and medical records. AED data were retrieved from the Emergency Medical Dispatch Centre (EMDC) and information on feedback mechanisms, energy waveform and energy level was downloaded from the applied AEDs.RESULTS: A total of 196 OHCAs had an AED applied prior to ambulance arrival; 62 of these (32%) provided audio visual (AV) feedback while no feedback was provided in 134 (68%). We found no difference in return of spontaneous circulation (ROSC) at hospital arrival according to AV-feedback; 34 (55%, 95% confidence interval (CI) [13-67]) vs. 72 (54%, 95% CI [45-62]), P = 1 (odds ratio (OR) 1.1, 95% CI [0.6-1.9]) or 30-day survival; 24 (39%, 95% CI [28-51]) vs. 53 (40%, 95% CI [32-49]), P = 0.88 (OR 1.1 (95% CI [0.6-2.0])). Moreover, we found no difference in converting rates among patients with initial shockable rhythm receiving one or more shocks according to AED energy waveform and energy level.CONCLUSIONS: No difference in survival after OHCA according to AED feedback mechanisms, nor any difference in converting rates according to AED waveform or energy levels was detected.

The number of people living with multimorbidity has increased dramatically during the last decades, which is associated with harms and costs for individuals as well as societies. This increase is explained by population longevity, but also by better medical treatment and tertiary prevention among patients with chronic diseases. However, the increased prevalence of multimorbidity may owe to the inconsistency of the definition of multimorbidity, which leaves room for both under- and overdiagnosis. The consequences of this overdiagnosis will plausibly have influence on the handling and daily clinical practice regarding the growing number of patients categorized as multimorbid. The theoretical background and hypotheses for the risks of overdiagnosis within multimorbidity concerns a lot of different aspects. Some of the aspects comprise different possibilities for overdiagnosis of diseases. Moreover, some of these diseases have different prognoses and have different meanings, values and treatment preferences for patients. Therefore, it could be relevant in a patient-centred approach for clinicians to conduct a diagnostic review and in dialogue with the patients find out which diagnoses are of importance and which could de-diagnosed. In this workshop we will invite participants to attend the discussion about drivers of overdiagnosis in relation to multimorbidity, and how we can study these problems scientifically. Furthermore, the aim of the workshop is to discuss whether a too broad definition of multimorbidity may result in more harm than benefit for the patients. Finally, we will discuss if diagnostic review in a primary health care setting is a relevant and appropriate approach among patients with multimorbidity who have been overdiagnosed with one or more diseases.

OBJECTIVE To examine long-term trends in marital stability, academic achievement, income, and socioeconomic status in patients with concussion. DESIGN AND SETTING Danish national register-based cohort study with 5 years of follow-up. PARTICIPANTS A total of 23 549 hospital-admitted or emergency-treated patients between 18 and 60 years of age with concussion (International Classification of Diseases, Tenth Revision [ICD-10] diagnosis S06.0) and 22 228 matching controls. MAIN MEASURES Outcomes were the differences between patients with concussion and controls in the change from injury date to 5 years postinjury in the dichotomized outcomes-martial stability, academic achievement, income, and socioeconomic status. RESULTS Fewer patients had high education (19.43%) compared with controls (23.96%) and the adjusted odds ratio (OR) of high education beyond the difference in prevalence at baseline became even lower at 5 years of follow-up (OR: 0.93, 95% confidence interval [CI]: 0.90-0.95). Patients were to a lesser extent gainfully employed (67.05%) compared with controls (77.32%) and had lower odds of being gainfully employed (OR: 0.83, 95% CI: 0.79-0.88), self-employed, leaders, or managers (OR: 0.89, 95% CI: 0.84-0.95) at 5 years postinjury, beyond differences at baseline. CONCLUSIONS Academic achievement and socioeconomic status are affected by concussion. There is no evidence that marital stability and income are affected. Supporting interventions should be considered those at risk of persistent symptoms.

BACKGROUND: We investigated the effect of economic assets on mortality in patients with dementia in a national cohort of elderly individuals aged 65 or older.OBJECTIVE: To examine the effect of economic assets on mortality in patients with dementia.METHODS: Incidence of dementia and all-cause mortality was analyzed with incidence rate ratios (IRR) in three different categories of economic assets by means of Cox regression models.RESULTS: A total of 874,246 individuals aged 65+ were included. The risk of receiving a dementia diagnosis was highest in the low economic asset group (IRR 1.19). Patients with dementia had a higher mortality compared to those without a diagnosis (IRR 2.85). The mortality in the dementia group was lowest in the high economic asset group (IRR 3.31). However, the increase associated with dementia was lowest within the low economic assets group (IRR 2.57).CONCLUSION: Mortality is increased with a dementia diagnosis and highest for the low economic asset group. However, the increase in mortality attributable to dementia was higher in the high economic assets group.

To analyze the association between change in HbA1c during the first 6 years after diagnosis of Type 2 diabetes mellitus (Type 2 DM) and incident micro- and macrovascular morbidity and mortality during 13 years thereafter. This is an observational study of the participants in the intervention arm of the randomized controlled trial Diabetes Care in General Practice (DCGP) in Denmark. 494 newly diagnosed persons with Type 2 DM aged 40 years and over with three or more measurements of HbA1c during six years of intervention were included in the analyses. Based on a regression line, fitted through the HbA1c-measurements from 1 to 6 years after diabetes diagnosis, glycaemic control was characterized by the one-year level of HbA1c after diagnosis, and the slope of the regression line. Outcomes were incident diabetes-related morbidity and mortality from 6 to 19 years after diabetes diagnosis. The association between change in HbA1c (the slope of the regression line) and clinical outcomes were assessed in adjusted Cox regression models. The median HbA1c level at year one was 60 (IQR: 52–71) mmol/mol or (7.65 (IQR: 6.91–8.62) %). Higher HbA1c levels one year after diagnosis were associated with a higher risk of later diabetes-related morbidity and mortality. An increase in HbA1c during the first 6 years after diabetes diagnosis was associated with later microvascular complications (HR per 1.1 mmol/mol or 0.1% point increase in HbA1c per year; 95% CI) = 1.14; 1.05–1.24). Change in HbA1c did not predict the aggregate outcome ‘any diabetes-related endpoint, all-cause mortality, diabetes-related mortality, myocardial infarction, stroke, or peripheral vascular diseases. We conclude that suboptimal development of glycaemic control during the first 6 years after diabetes diagnosis was an independent risk factor for microvascular complications during the succeeding 13-year follow-up, but not for mortality or macrovascular complications.

BACKGROUND: The aim was to explore the association between retrospectively assessed psychosocial working conditions during working life and prospectively assessed risk of sickness absence and disability pension among older workers.METHODS: The prospective risk of register-based long-term sickness absence (LTSA) and disability pension was estimated from exposure to 12 different psychosocial work characteristics during working life among 5076 older workers from the CAMB cohort (Copenhagen Aging and Midlife Biobank). Analyses were censored for competing events and adjusted for age, gender, physical work environment, lifestyle, education, and prior LTSA.RESULTS: LTSA was predicted by high levels of cognitive demands (HR 1.31 (95% CI 1.10-1.56)), high levels of emotional demands (HR 1.26 (95% CI 1.07-1.48)), low levels of influence at work (HR 1.30 (95% CI 1.03-1.64)), and high levels of role conflicts (HR 1.34 (95% CI 1.09-1.65)). Disability pension was predicted by low levels of influence at work (HR 2.73 (95% CI 1.49-5.00)) and low levels of recognition from management (HR 2.04 (95% CI 1.14-3.67)).CONCLUSIONS: This exploratory study found that retrospectively assessed high cognitive demands, high and medium emotional demands, low influence at work, low recognition from management, medium role clarity, and high role conflicts predicted LTSA and/or disability pension.

ObjectiveTo determine the prospective association between retrospectively assessed physical work environment during working life and prospectively assessed sickness absence and labour market exit among older workers.MethodsUsing Cox regression analyses we estimated the 4-year to 6-year prospective risk of register-based long-term sickness absence (LTSA), disability pension, early retirement and unemployment from exposure to different physical work environmental factors during working life among 5076 older workers (age 49–63 at baseline) from the Copenhagen Aging and Midlife Biobank cohort.ResultsVery hard physical work throughout working life was a risk factor for LTSA (HR 1.66,95% CI 1.32 to 2.07), disability pension (HR 2.21,95% CI 1.04 to 4.72) and early retirement (HR 1.57,95% CI 1.13 to 2.17). Both short-term (ConclusionsRetrospectively assessed hard physical work during working life and exposure to several factors in the physical work environment, especially heavy lifting, were important for labour market exit and sickness absence. This study underscores the importance of reducing physical work exposures throughout the working life course for preventing sickness absence and premature exit from the labour market.

Introduction We aim to determine the prospective association of different physical capacity tests with health related labour market outcomes among older workers. Methods The prospective risk of register-based long-term sickness absence (LTSA) and disability pension from measured musculoskeletal capacity (jump performance, postural balance, sit-to-stand, explosive muscle strength, and maximal strength of the hand, back and abdominal muscles) and cardiovascular capacity (lung function and aerobic fitness) were estimated among 5076 older workers from the Copenhagen Ageing and Midlife Biobank. Time-to-event analyses were censored for competing events and adjusted for age, gender, physical and psychosocial work environment, lifestyle, socioeconomic position and previous LTSA. Results Low physical capacity in many of the tests (less than 1SD below mean) predicted risk of LTSA and disability pension. Specifically, low aerobic fitness (HR 5.9), low jump performance (HR 2.7) and low abdominal muscle strength (HR 3.3) predicted risk of disability pension. A dose-response association was observed between number of musculoskeletal capacity tests with low performance and disability pension and LTSA - with the risk-estimate for disability pension being 7.6 when low capacity was present in ≥5 musculoskeletal capacity tests. Population attributable risks for disability pension and LTSA from poor musculoskeletal capacity were 33% and 8%, respectively. Conclusions Poor musculoskeletal and cardiovascular capacity in midlife increased the risk for LTSA and disability pension. Promoting physical capability to a normal level among older workers with low capacity may have the opportunity to prevent premature exit from the labour market.

Background On the Danish island of Bornholm an intervention was carried out during 2008–2010 aiming at increasing out-of-hospital cardiac arrest (OHCA) survival. The intervention included mass media focus on resuscitation and widespread educational activities. The aim of this study was to compare the bystander BLS rate and survival after OHCA on Bornholm in a 3-year follow-up period after the intervention took place. Methods Data on OHCA on Bornholm were collected from September 28th, 2010 to September 27th, 2013 and compared to data from the intervention period, September 28th, 2008 to September 27th, 2010. Results The bystander BLS rate for non-EMS witnessed OHCAs with presumed cardiac aetiology was significantly higher in the follow-up period (70% [95% CI 61–77] vs. 47% [95% CI 37–57], p = 0.001). AEDs were deployed in 22 (18%) cases in the follow-up period and a shock was provided in 13 cases. There was no significant change in all-rhythm 30-day survival for non-EMS witnessed OHCAs with presumed cardiac aetiology (6.7% [95% CI 3–13] in the follow-up period; vs. 4.6% [95% CI 1–12], p = 0.76). Conclusion In a 3-year follow-up period after an intervention engaging laypersons in resuscitation through mass education in BLS combined with a media focus on resuscitation, we observed a persistent significant increase in the bystander BLS rate for all OHCAs with presumed cardiac aetiology. There was no significant difference in 30-day survival.

ObjectivesSickness absence after mild traumatic brain injury (mTBI) is frequent due to postconcussive symptoms. We examined labour market attachment following mTBI up to 5 years postinjury.Design and settingNationwide cohort study with register follow-up.ParticipantsPatients between 18 and 60 years with mTBI (International Classification of Diseases, version 10 diagnosis S06.0) were extracted from the Danish National Patient Register (n=19 732). Controls were matched on sex, age and municipality (n=18 640). Patients with spinal cord and column injuries, traumatic brain injury and concussions 5 years preinjury or as secondary diagnosis to the concussion in the inclusion period were excluded.Primary and secondary outcome measuresData were extracted from the Danish Register for Evaluation of Marginalization. Primary outcome was ‘not attending ordinary work’ defined as receiving any social transfer payment. Secondary outcomes were health-related benefits, limited attachment to the labour market, permanent lack of attachment to the labour market and death.Results5 years after diagnosis, 43% of patients were not attending ordinary work. The odds increased from 6 months (OR 1.30, 95% CI 1.24 to 1.36) to 5 years (OR 1.54, 95% CI 1.45 to 1.63). The odds of health-related benefits were 32% (OR 1.32, 95% CI 1.22 to 1.42) at 6 months and 22% (OR 1.22, 95% CI 1.12 to 1.33) at 5 years. Limited attachment to the labour market showed increased odds at 5 years (OR 1.38, 95% CI 1.27 to 1.51) and the odds of permanent lack of attachment to the labour market were higher for patients compared with controls (OR 2.59, 95% CI 2.30 to 2.92). Death was more than two times higher at 5 years postinjury (OR 2.62, 95% CI 2.10 to 3.26).Conclusions43% of concussed patients were not attending ordinary work 5 years postinjury and received health and social transfer benefits. We conclude that mTBI has a long-term impact on labour market attachment. Prevention and treatment of persisting postconcussive symptoms should be considered.Trial registration numberNCT03214432; Results

Carcinomas of unknown primary origin constitute 3% to 5% of all newly diagnosed metastatic cancers, with the primary source difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification of the tumor; patients with metastases of unknown origin have poor prognosis and short survival. Because miRNA expression is highly tissue specific, the miRNA profile of a metastasis may be used to identify its origin. We therefore evaluated the potential of miRNA profiling to identify the primary tumor of known metastases. Two hundred eight formalin-fixed, paraffin-embedded samples, representing 15 different histologies, were profiled on a locked nucleic acid-enhanced microarray platform, which allows for highly sensitive and specific detection of miRNA. On the basis of these data, we developed and cross-validated a novel classification algorithm, least absolute shrinkage and selection operator, which had an overall accuracy of 85% (CI, 79%-89%). When the classifier was applied on an independent test set of 48 metastases, the primary site was correctly identified in 42 cases (88% accuracy; CI, 75%-94%). Our findings suggest that miRNA expression profiling on paraffin tissue can efficiently predict the primary origin of a tumor and may provide pathologists with a molecular diagnostic tool that can improve their capability to correctly identify the origin of hitherto unidentifiable metastatic tumors and, eventually, enable tailored therapy.

Objectives: The aim of this study was to determine the prospective association of cumulative mechanical exposure during working life with health-related labor market outcomes. Methods: This prospective cohort study combines data from 5076 older workers (age 49-63 years) from the Copenhagen Aging and Midlife Biobank with a job exposure matrix and a national register containing information on social transfer payment. By coding individual job histories from the Danish version of ISCO-codes (International Standard Classification of Occupations), we calculated cumulative occupational mechanical exposures from a JEM for ton-years (lifting 1000 kg each day in one year), lifting-years (lifting loads weighing ≥20 kg >10 times each day in one year), kneeling-years (kneeling for one hour each day in one year) and vibration-years (whole-body vibration for one hour each day in one year). Cox-regression analyses estimated the relative risk of register-based long-term sickness absence (LTSA) and disability pension with cumulative occupational mechanical exposures throughout working life. Analyses were censored for competing events and adjusted for multiple confounders.Results: During the follow-up period, 970 persons (19.3%) had ≥1 episode of LTSA and 85 persons (1.7%) were granted a disability pension. Number of ton-, lifting- and kneeling-years showed an exposure-response association with increased risk of LTSA (PConclusions: Cumulative occupational mechanical exposures during working life - such as lifting and kneeling work - increased the risk of LTSA. Importantly, being exposed to lifting increased the risk of disability pension.

We investigate whether job loss as the result of displacement causes hospitalization for stress-related diseases which are widely thought to be associated with unemployment. In doing this, we use much better data than any previous investigators. Our data are a random 10% sample of the male population of Denmark for the years 1981-1999 with full records on demographics, health and work status for each person, and with a link from every working person to a plant. We use the method of 'matching on observables' to estimate the counter-factual of what would have happened to the health of a particular group of displaced workers if they had not in fact been displaced. Our results indicate unequivocally that being displaced in Denmark does not cause hospitalization for stress-related disease. An analysis of the power of our test suggests that even though we are looking for a relatively rare outcome, our data set is large enough to show even quite small an effect if there were any. Supplementary analyses do not show any causal link from displacement or unemployment to our health outcomes for particular groups that might be thought to be more susceptible.

Background: As average life span increases, elderly will account for an increasing proportion of the total population in most parts of the world. Thus, initiatives to retain older workers at the labor market are becoming increasingly important. This study will investigate the influence of physical and psychosocial work environment throughout working life and physical and cognitive capacity in midlife on labor market attachment among older workers. Methods/Design: Approximately 5000 participants (aged 50-60 years) from the Copenhagen Aging and Midlife Biobank (CAMB) will be followed prospectively in a national register (DREAM), containing information on a week-to-week basis about social transfer payments for about 5 million Danish residents. Using Cox regression, we will model the risk of long-term sickness absence, disability pension, early retirement and unemployment within a 4 to 6 year period from the baseline measurement as a function of the following predictors: 1) physical work demands throughout working life, 2) psychosocial working conditions throughout working life, 3) physical capacity in midlife, 4) cognitive capacity in midlife. Estimates will be adjusted for age, sex, lifestyle, socioeconomic position, chronic disease and long-term sickness absence prior to baseline. Discussion: The project will generate new knowledge on risk factors for loss of labor market attachment. The results will potentially contribute in identifying factors that could be targeted in future interventions for maintaining a longer and healthier working life among older workers.

Background Video-based self-instruction (VSI) with a 24-min DVD and a personal resuscitation manikin solves some of the barriers associated with traditional basic life support (BLS) courses. No accurate assessment of the actual improvement in skills after attending a VSI course has been determined, and in this study we assess the skill improvement in laypersons undergoing VSI. Methods The BLS skills of 68 untrained laypersons (high school students, their teachers and persons excluded from mainstream society) were assessed using the Laerdal ResusciAnne and PC Skill Reporting System 2.0 in a 3 min test. A total score (12–48 points) was calculated and 12 different variables were recorded. The participants attended a 24-min VSI course (MiniAnne, Laerdal) and took home the DVD and manikin for optional subsequent self-training. We repeated the test 3½–4 months later. Results There was a significant increase in the total score (p

The clinical, humanistic and economic consequences associated with haemophilia and inhibitors are considerable. Primary treatment for mild-to-moderate bleeding disorders in such patients is recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (APCC). The aims of this study were to identify, review and evaluate the quality of the published literature on the relative cost-effectiveness of rFVIIa and APCC in treating haemophilia patients with inhibitors. The review concentrates on model type, design and assumptions, and results. The results of this study suggest that rFVIIa may be the cost-effective alternative to treatment with APCC. In seven out of the nine studies, rFVIIa had the lower average treatment cost. The difference in average treatment cost to resolve a bleed, between rFVIIa and APCC in these seven studies, ranged from $3000 to $17 000. The adapted modelling framework is similar in all the economic models reviewed, suggesting clinical acceptability of the approach used. The estimates of efficacy varied between the models, especially for APCC. The efficacy for APCC derived from retrospective studies was lower than reported in the literature. Sensitivity analysis was undertaken in the majority of the economic analyses and the results were found to be robust to realistic parameter variations. Only one of the studies was a cost-utility study, showing the lack of measuring health status within this area. This systematic review showed that models based on different sources of data produced fairly similar robust results despite differences in the estimates of efficacy, average dosage required, and unit costs. However, ideally there should be a systematic approach to identifying the relevant data.

The primary treatment for mild-to-moderate bleeding disorders in hemophilia is either recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrate (aPCC). The efficacy of both products has been evaluated in individual studies; however, there has not been an overall review to compare the efficacy from these individual studies of rFVIIa and aPCC. Our aim is to establish robust estimates of the efficacy, speed of bleed resolution, and adverse event profile of both rFVIIa and aPCC.A systematic review was conducted of the relevant literature.We identified 11 open-label cohort studies, six randomized clinical trials, including two head-to-head clinical trials, and a meta-analysis. The definition of efficacy varies between these studies, but is usually a composite measure of definite pain relief, reduction in the size of the hemorrhage, and cessation of bleeding. The individual making the interpretation of efficacy and the time from treatment initiation to recording the efficacy endpoint also varies across the studies. Overall, estimates of efficacy from randomized clinical trials using dosing regimens in line with the guidelines are higher for rFVIIa (81%-91%) than for aPCC (64%-80%). Conclusions from a meta-analysis suggest that treatment with rFVIIa may be associated with a faster time to joint bleed resolution than aPCC due to higher efficacy levels at different time points. The results from a comparative trial support the improved efficacy rates associated with rFVIIa compared with aPCC.The wide variations in definitions of efficacy and study methods make comparison of results across studies difficult. Further head-to-head trials should incorporate a standardized measurement for defining efficacy.

The objective of this study was to model the economic impact of optimal dosing of immune tolerance induction (ITI) in haemophilia patients with inhibitors. Evidence based research suggests that, in the right patient population characterised by ITI risk status, the use of high-dose ITI regimen in 'poor risk' patients, and the low-dose regimen in 'good risk' patients, would be the cost effective strategy. The model also explored the impact of anamnestic response (AR), a phenomenon which worsens patients' ITI risks.A cost-minimisation technique was used to compare the cost of managing inhibitor patients whose bleeds were managed pre-ITI with an immunogenic bypassing agent, activated prothrombin complex concentrate (APCC), with patients previously on a non-immunogenic product, recombinant activated factor VII (rFVIIa). Patients were subsequently offered a low-dose or high-dose ITI regime depending on their ITI risk status. The study perspective was that of the United Kingdom NHS, hence, all resources used were based on UK costs.The model estimated the mean cost of managing inhibitor patients from detection of titres through ITI to be 959,250.39 pound sterling and 770,834.17 pound sterling in the APCC and rFVIIa treatment options, respectively. Meanwhile, the costs per effectively tolerised patients were 1,505,279 pound sterling and 1,196,706 pound sterling for APCC and rFVIIa treated patients, respectively. Of the incremental cost in the APCC-treated patients in the model, 129,367 pound sterling (68%) represents additional ITI cost attributable to anamnestic response to earlier treatment with an immunogenic bypassing agent (APCC).The study concludes that decreasing factor VIII usage during ITI, through the identification and management of 'good risk' ITI patients with low-dose protocol, while managing 'poor risk' patients with high-dose regimen, will significantly lower the cost of ITI. Furthermore, avoiding AR prior to ITI by using non-immunogenic bypassing agents to manage spontaneous bleeds also has the potential for significant cost savings.

Objectives: Our aim was to study associations between physical exposures throughout working life and physical function measured as chair-rise performance in midlife. Methods: The Copenhagen Aging and Midlife Biobank (CAMB) provided data about employment and measures of physical function. Individual job histories were assigned exposures from a job exposure matrix. Exposures were standardised to ton-years (lifting 1000 kg each day in 1 year), stand-years (standing/walking for 6 h each day in 1 year) and kneel-years (kneeling for 1 h each day in 1 year). The associations between exposure-years and chair-rise performance (number of chair-rises in 30 s) were analysed in multivariate linear and non-linear regression models adjusted for covariates. Results: Mean age among the 5095 participants was 59 years in both genders, and, on average, men achieved 21.58 (SD=5.60) and women 20.38 (SD=5.33) chair-rises in 30 s. Physical exposures were associated with poorer chair-rise performance in both men and women, however, only associations between lifting and standing/walking and chair-rise remained statistically significant among men in the final model. Spline regression analyses showed non-linear associations and confirmed the findings. Conclusions: Higher physical exposure throughout working life is associated with slightly poorer chair-rise performance. The associations between exposure and outcome were non-linear.

Identification of the primary tumor site in patients with metastatic cancer is clinically important, but remains a challenge. Hence, efforts have been made towards establishing new diagnostic tools. Molecular profiling is a promising diagnostic approach, but tissue heterogeneity and inadequacy may negatively affect the accuracy and usability of molecular classifiers. We have developed and validated a microRNA-based classifier, which predicts the primary tumor site of liver biopsies, containing a limited number of tumor cells. Concurrently we explored the influence of surrounding normal tissue on classification. MicroRNA profiling was performed using quantitative Real-Time PCR on formalin-fixed paraffin-embedded samples. 278 primary tumors and liver metastases, representing nine primary tumor classes, as well as normal liver samples were used as a training set. A statistical model was applied to adjust for normal liver tissue contamination. Performance was estimated by cross-validation, followed by independent validation on 55 liver core biopsies with a tumor content as low as 10%. A microRNA classifier developed, using the statistical contamination model, showed an overall classification accuracy of 74.5% upon independent validation. Two-thirds of the samples were classified with high-confidence, with an accuracy of 92% on high-confidence predictions. A classifier trained without adjusting for liver tissue contamination, showed a classification accuracy of 38.2%. Our results indicate that surrounding normal tissue from the biopsy site may critically influence molecular classification. A significant improvement in classification accuracy was obtained when the influence of normal tissue was limited by application of a statistical contamination model.

CupPrint® is a genomic signature able to identify 47 different cancer types. The aim of our study was to compare the accuracy of this genomic signature to that of a full clinical work-up in diagnosing the primary tumour site. Patients with newly diagnosed, untreated metastatic tumours were eligible for this trial. The clinical work-up and gene expression profiling on a biopsy from a metastatic site were started at the same time. The study was planned using a one-stage Fleming design. Patients in whom no primary site was diagnosed by the clinical work-up were excluded. Out of the 67 patients registered, the primary site was identified by clinical work-up in 36 patients, and diagnosis with CupPrint was obtained in 53. There were 31 evaluable patients with both clinical and CupPrint diagnoses, and out of these a similar diagnosis was obtained in 11 patients, i.e. the concordance rate was 35% (95% confidence interval: 19-55%). The median time to diagnosis through the clinical work-up was 48 days, and 10 days with CupPrint (P0·001). We concluded that in patients with newly diagnosed metastatic tumours, CupPrint has low accuracy in diagnosing the primary cancer site.

Aims: In epidemiological studies exposure assessment based on questionnaires is the most cost-effective method. A question about lifetime exposure to occupational physical activity (OPA) was used in a population-based survey (part of the Copenhagen Aging and Midlife Biobank, CAMB). The aim of the study was to validate this question through a three-step process. Methodology: Firstly, the response process was studied by cognitive interviewing of 7 persons. Secondly, 64 persons participated in semi-structured interviews about their worklife, and expert judgments of exposure to OPA were compared with questionnaire-data. Exposure was 20 years of work in one of four categories of OPA: sedentary, standing and walking, moderate or high OPA. Kappa values were calculated for agreement and interpreted according to Landis and Koch’s criteria. Agreement was visualized in Bland- Altman plots. Thirdly, intra- and inter-rater reliability of expert judgments was tested. Results: Response process: The question had a complicated instruction, and the respondents found it hard to remember, categorize, and summate exposures. Semistructured interviews: Kappa value for exposure to sedentary work was ‘substantial’ (0.71) but ‘fair’ for the other categories of OPA (0.27-0.29). Agreement between questionnaire and interview was higher in sedentary jobs and jobs with high OPA. Intra-rater reliability of expert judgments was ‘substantial’ or ‘moderate’ (0.60-0.71). Inter-rater reliability was high in sedentary jobs but lower in the more active jobs. Conclusion: Self-reports of lifetime exposure to sedentary work are valid in the CAMB cohort, whereas the validity of self-reports of exposure to high levels of occupational physical activity (OPA) are questionable. Thorough pre-testing of questions about lifetime OPA is recommended.

BackgroundPhysical function is essential for performing most aspects of daily life and musculoskeletal aging leads to a decline in physical function. The onset and rate of this process vary and are influenced by environmental, genetic, and hormonal factors. Although everyone eventually experiences musculoskeletal aging, it is beneficial to study the factors that influence the aging process in order to prevent disability. The role of occupational physical activity in the musculoskeletal aging process is unclear. In the past, hard physical work was thought to strengthen the worker, but current studies in this field fail to find a training effect in jobs with a high level of occupational physical activity. ObjectiveThe aim of this study is to examine the influence of lifetime occupational physical activity on physical function in midlife. The study follows the “occupational life-course perspective,” emphasizing the importance of occupational exposures accumulated throughout life on the musculoskeletal aging process taking socioeconomic and lifestyle factors into consideration. MethodsThis study is a retrospective cohort study including a cross-sectional measurement of physical function in 5000 middle-aged Danes. Data was obtained from the Copenhagen Aging and Midlife Biobank (CAMB) which is based on three existing Danish cohorts. Using questionnaire information about the five longest-held occupations, the job history was coded from the Danish version of the International Standard Classification of Occupations (D-ISCO 88) and a job exposure matrix containing information about occupational physical activity in Danish jobs was applied to the dataset. The primary outcomes are three tests of physical function: handgrip strength, balance, and chair rise. In the analyses, we will compare physical function in midlife according to accumulated exposure to high levels of occupational physical activity. ConclusionsWe have a unique opportunity to study the influence of work on early musculoskeletal aging taking other factors into account. In this study, the “healthy worker effect” is reduced due to inclusion of people from the working population and people who are already retired or have been excluded from the labor market. However, low participation in the physical tests can lead to selection bias.

Learning Objectives After completing this course, the reader will be able to: Compare the diagnostic performances of 18F-FDG PET/CT and conventional CT with respect to their ability to detect primary tumor sites in carcinoma of unknown primary patients with extracervical metastases.Describe the rate of identification of primary tumor sites using 18F-FDG PET/CT and conventional CT. CME This article is available for continuing medical education credit at CME.TheOncologist.com Background. The aim of the present study was to evaluate prospectively the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and conventional CT regarding the ability to detect the primary tumor site in patients with extracervical metastases from carcinoma of unknown primary (CUP) site. Patients and Methods. From January 2006 to December 2010, 136 newly diagnosed CUP patients with extracervical metastases underwent 18F-FDG PET/CT. A standard of reference (SR) was established by a multidisciplinary team to ensure that the same set of criteria were used for classification of patients, that is, either as CUP patients or patients with a suggested primary tumor site. The independently obtained suggestions of primary tumor sites using PET/CT and CT were correlated with the SR to reach a consensus regarding true-positive (TP), true-negative, false-negative, and false-positive results. Results. SR identified a primary tumor site in 66 CUP patients (48.9%). PET/CT identified 38 TP primary tumor sites and CT identified 43 TP primary tumor sites. No statistically significant differences were observed between 18F-FDG PET/CT and CT alone in regard to sensitivity, specificity, and accuracy. Conclusion. In the general CUP population with multiple extracervical metastases 18F-FDG PET/CT does not represent a clear diagnostic advantage over CT alone regarding the ability to detect the primary tumor site.

Background Automated External Defibrillators (AEDs) are known to increase survival after out-of-hospital cardiac arrest (OHCA). The aim of this study was to examine the use and benefit of public-access defibrillation (PAD) in a nation-wide network. We primarily sought to assess survival at 1 month but information about the circumstances of each OHCA is provided as well. Methods In this 28-month study, we assessed the use of 807 AEDs in Denmark. When an AED was deployed information about the circumstances of OHCA, the bystander, the AED and the victim's condition was obtained. Results An AED was connected to an OHCA victim prior to the arrival of Emergency Medical Services (EMS) in 48 instances. Ten percent of bystanders were off-duty healthcare professionals. Shockable arrests (N = 31, 70%) were significantly more likely to be witnessed (94% vs. 54%) to occur at sports facilities (74% vs. 31%), in relation to exercise (42% vs. 0%), and with improved 30-day survival (69% vs. 15%, p = 0.001). Among those presenting with a shockable rhythm, 20 (65%) had Return of Spontaneous Circulation upon arrival of EMS and 8 (26%) were conscious, which emphasizes the diagnostic value of ECG downloads from AEDs. Survival could be determined in 42 of 44 patients with OHCA of cardiac origin, and was 52% (n = 22, 95% CI [38–67]) and the Cerebral Performance Category was 1 (Good Cerebral Performance) in all survivors. Conclusion With a 30-day neurologically intact survival of 69% for patients with shockable rhythms, this study provides further evidence of the lifesaving potential of PAD.

Background Survival after out-of-hospital cardiac arrest (OHCA) is influenced by each link in the chain of survival. On the Danish island of Bornholm (population 42,000, area 588km 2 ) none survived an OHCA in 2001–2003. Therefore, we designed a multifaceted community-based approach aiming at strengthening each link in the chain of survival. The purpose of this study was to evaluate the effect of implementation of the intervention on bystander basic life support (BLS) rates and survival to hospital discharge after OHCA. Methods Laypersons completed 24-min DVD-based-self-instruction BLS courses in schools and workplaces or 4-h BLS/automated external defibrillator (AED) courses. The local television station had broadcasts about resuscitation. The ambulance personnel were trained and the staff at the island hospital completed BLS courses or more advanced courses. Results During 2 years 9226 people (22% of the population) completed the short course and 2453 (6% of the population) completed the 4-h course. The number of AEDs increased from 3 to 147. The bystander BLS rate for OHCAs with a presumed cardiac aetiology ( N =96, incidence 114/100,000 person-years) was 47% [95% CI 30–50] and for witnessed OHCAs ( N =35) it increased significantly from 22% (2004) to 74% [95% CI 58–86]. The AEDs were deployed in 9 cases. Survival to discharge for all-rhythms OHCA was 5.4% [95% CI 2–12], and for witnessed ventricular fibrillation ( N =17) 18% [95% CI 5–42]. Conclusion Strengthening all links in the chain of survival was associated with significant increases in bystander BLS rates and survival after OHCA on a rural island.

Background. Carcinoma of unknown primary (CUP) represents a heterogeneous group of metastatic malignancies for which no primary tumor site can be identified after extensive diagnostic workup. Failure to identify the primary site may negatively influence patient management. The aim of this review was to evaluate 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) as a diagnostic tool in patients with extracervical CUP. Materials and Methods. A comprehensive literature search was performed and four publications were identified (involving 152 patients) evaluating 18F-FDG PET/CT in CUP patients with extracervical metastases. All studies were retrospective and heterogeneous in inclusion criteria, study design, and diagnostic workup prior to 18F-FDG PET/CT. Results. 18F-FDG PET/CT detected the primary tumor in 39.5% of patients with extracervical CUP. The lung was the most commonly detected primary tumor site (∼50%). The pooled estimates of sensitivity, specificity, and accuracy of 18F-FDG PET/CT in the detection of the primary tumor site were 87%, 88%, and 87.5%, respectively. Conclusions. The present review of currently available data indicates that 18F-FDG PET/CT might contribute to the identification of the primary tumor site in extracervical CUP. However, prospective studies with more uniform inclusion criteria are required to evaluate the exact value of this diagnostic tool.

The present study was conducted to evaluate the efficacy and toxicity of a combination of paclitaxel, cisplatin and gemcitabine in patients with carcinoma of unknown primary site (CUP).Patients with CUP, ECOG performance status 0-1 and age between 18 and 65 years old were treated with paclitaxel 175 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1 and gemcitabine 1000 mg/m(2) day 1 and 8 in a three-week schedule.Ninety-eight patients were enrolled between 1998 and 2008. Ninety-one patients had target lesions according to the RECIST guidelines. The overall response rate was 42.9% (39 patients), including five complete responses (5.5%) and 34 partial responses (37.4%). The median survival time was 10.7 months, and the survival rates at one and two years were 42% and 14%, respectively. The most frequent grade 3 or more adverse events were neutropenia and thrombocytopenia. There were 3 treatment-related deaths.Combination of paclitaxel, cisplatin and gemcitabine is an active regimen in patients with CUP with response and survival rates at least similar to other platinum- and taxane-containing regimens. The treatment was well tolerated by most patients although neutropenia and thrombocytopenia were relatively common. The present regimen represents an attractive regimen in younger CUP patients with a good performance status.

Background. Treatment of patients with carcinoma of unknown primary site (CUP) remains a challenge, and no effective second-line treatment has been identified. In CUP patients who are non-responsive or relapse early after first-line platinum/taxane-based regimens, it is likely that gastrointestinal (GI) tract tumours may be overrepresented. These patients could be candidates for GI tract-directed therapy. We here report the results obtained with oxaliplatin and capecitabine as second-line therapy in 25 recurrent/refractory CUP patients following first-line treatment with paclitaxel, cisplatin and gemcitabine. Patients and methods. Patients received capecitabine orally (1000 mg/m 2 ) twice daily, days 1–14, and oxaliplatin (130 mg/m 2 ) intravenously on day 1 in a three-week schedule. Results. Twenty-five CUP patients received a median of three cycles of capecitabine and oxaliplatin as second-line treatment. Histopathological assessments suggested the primary site to be of GI tract origin in the majority of the patients (76%). We found an objective response rate of 13%, a median progression-free survival and overall survival rate of 2.3 and 3.9 months, respectively, and 32% of patients alive at one year after initiation of second-line therapy. The regimen was well tolerated by most patients. Conclusions. This study, demonstrates that there is still a significant need for improved second-line therapy in CUP patients. Carcinoma of unknown primary site (CUP) accounts for 3–5% of all cancer diagnoses and is characterised by early dissemination, uncommon metastatic sites, and usually a poor prognosis [1,2]. The majority of CUP patients have adenocarcinomas or poorly differentiated carcinomas. Treatment of the unfavourable subset, i.e. the majority, of CUP patients remains a challenge, and an optimal first-line treatment is still not identified. Regimens with platinum/taxane result in some of the highest response rates and longest median overall survival [3]. However, these regimens are not optimal if the primary tumour is located in the gastrointestinal (GI) tract. In these cases, agents like 5-fluorouracil, oxaliplatin, irinotecan and gemcitabine are recommended. GI-tract regimens have been evaluated in the first-line setting in CUP patients, with lower response rates (mean 22%)

Mobilized peripheral blood stem and progenitor cells (PBPCs) are increasingly used to restore hematopoiesis after myeloablative treatment. To obtain a sufficient number of CD34(+) cells, many studies have focused on the improvement of the collection technique during the leukapheresis procedure (LP), and so-called large-volume leukapheresis (LVL) procedures have been developed. Such procedures can be performed by extending the duration of the LP and/or by increasing the inlet flow rate. However, no previous studies have compared the efficiency of these procedures. In the present study, we compared the kinetics of PBPCs recruitment (including CD34(+) cell subsets), the PBPCs yield, and the collection efficiency as well as the overall feasibility of the procedures during a single LVL performed by standard (group I) (median 85 ml/min; range 50-97 ml/min) and high inlet flow rates (group II) (median 130 ml/min; range 110-150 ml/min). Seven patients with hematological malignancies were enrolled and allocated to each group. The patients' blood volumes (BV) were processed four times. The apheresis product (AP) was collected in four separate bags, which were changed every time one BV had been processed. The CD34(+) cell number and CD34(+) cell subsets were assessed in the four collection bags and in peripheral blood (PB) before every time one BV had been processed and after the leukapheresis. The CD34(+) cell yield exceeded the pre-apheresis CD34(+) cell number per ml BV in 6 out of 7 patients in group I and in 3 out of 7 patients in group II. In group II, the recruitment of CD34(+) cells from the bone marrow (BM) to PB starts in the second collection period--as early as 30-60 min after initiating the procedure. No exhaustion in the recruitment was observed in the two groups for at least 5 h during the leukapheresis, and all CD34(+) cell subsets were recruited at a steady rate. However, the collection efficiency in group II was only half of that in group I. In addition, we experienced many technical problems during the leukapheresis in group II. Thus, in 4 out of 7 patients in this group, it was not possible to perform the maximal inlet flow rate because of catheter problems. In conclusion, due to the technical problems associated with the high inlet flow rate procedure and the fact that the relative number of CD34(+) cells harvested and recruited during the leukapheresis was higher in group I than II and, also reflected an approximately two-fold higher collection efficiency, we recommend that LVL be performed by standard inlet flow rate.

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