Christian Kronborg

Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled trial

BACKGROUND Video-assisted thoracoscopic surgery (VATS) is used increasingly as an alternative to thoracotomy for lobectomy in the treatment of early-stage non-small-cell lung cancer, but remains controversial and worldwide adoption rates are low. Non-randomised studies have suggested that VATS reduces postoperative morbidity, but there is little high-quality evidence to show its superiority over open surgery. We aimed to investigate postoperative pain and quality of life in a randomised trial of patients with early-stage non-small-cell lung cancer undergoing VATS versus open surgery. METHODS We did a randomised controlled patient and observer blinded trial at a public university-based cardiothoracic surgery department in Denmark. We enrolled patients who were scheduled for lobectomy for stage I non-small-cell lung cancer. By use of a web-based randomisation system, we assigned patients (1:1) to lobectomy via four-port VATS or anterolateral thoracotomy. After surgery, we applied identical surgical dressings to ensure masking of patients and staff. Postoperative pain was measured with a numeric rating scale (NRS) six times per day during hospital stay and once at 2, 4, 8, 12, 26, and 52 weeks, and self-reported quality of life was assessed with the EuroQol 5 Dimensions (EQ5D) and the European Organisation for Research and Treatment of Cancer (EORTC) 30 item Quality of Life Questionnaire (QLQ-C30) during hospital stay and 2, 4, 8, 12, 26, and 52 weeks after discharge. The primary outcomes were the proportion of patients with clinically relevant moderate-to-severe pain (NRS ≥3) and mean quality of life scores. These outcomes were assessed longitudinally by logistic regression across all timepoints. Data for the primary analysis were analysed by modified intention to treat (ie, all randomised patients with pathologically confirmed non-small-cell lung cancer). This trial is registered with ClinicalTrials.gov, number NCT01278888. FINDINGS Between Oct 1, 2008, and Aug 20, 2014, we screened 772 patients, of whom 361 were eligible for inclusion and 206 were enrolled. We randomly assigned 103 patients to VATS and 103 to anterolateral thoracotomy. 102 patients in the VATS group and 99 in the thoracotomy group were included in the final analysis. The proportion of patients with clinically relevant pain (NRS ≥3) was significantly lower during the first 24 h after VATS than after anterolateral thoracotomy (VATS 38%, 95% CI 0·28-0·48 vs thoracotomy 63%, 95% CI 0·52-0·72, p=0·0012). During 52 weeks of follow-up, episodes of moderate-to-severe pain were significantly less frequent after VATS than after anterolateral thoracotomy (p<0·0001) and self-reported quality of life according to EQ5D was significantly better after VATS (p=0·014). By contrast, for the whole study period, quality of life according to QLQ-C30 was not significantly different between groups (p=0·13). Postoperative surgical complications (grade 3-4 adverse events) were similar between the two groups, consisting of prolonged air leakage over 4 days (14 patients in the VATS group vs nine patients in the thoracotomy group), re-operation for bleeding (two vs none), twisted middle lobe (one vs three) or prolonged air leakage over 7 days (five vs six), arrhythmia (one vs one), or neurological events (one vs two). Nine (4%) patients died during the follow-up period (three in the VATS group and six in the thoracotomy group). INTERPRETATION VATS is associated with less postoperative pain and better quality of life than is anterolateral thoracotomy for the first year after surgery, suggesting that VATS should be the preferred surgical approach for lobectomy in stage I non-small-cell lung cancer. FUNDING Simon Fougner Hartmanns Familiefond, Guldsmed AL & D Rasmussens Mindefond, Karen S Jensens legat, The University of Southern Denmark, The Research Council at Odense University Hospital, and Department of Cardiothoracic Surgery, Odense University Hospital.

Cost-effectiveness of early intervention in first-episode psychosis: economic evaluation of a randomised controlled trial (the OPUS study)

BACKGROUND Information about the cost-effectiveness of early intervention programmes for first-episode psychosis is limited. AIMS To evaluate the cost-effectiveness of an intensive early-intervention programme (called OPUS) (trial registration NCT00157313) consisting of enriched assertive community treatment, psychoeducational family treatment and social skills training for individuals with first-episode psychosis compared with standard treatment. METHOD An incremental cost-effectiveness analysis of a randomised controlled trial, adopting a public sector perspective was undertaken. RESULTS The mean total costs of OPUS over 5 years (€123,683, s.e. = 8970) were not significantly different from that of standard treatment (€148,751, s.e. = 13073). At 2-year follow-up the mean Global Assessment of Functioning (GAF) score in the OPUS group (55.16, s.d. = 15.15) was significantly higher than in standard treatment group (51.13, s.d. = 15.92). However, the mean GAF did not differ significantly between the groups at 5-year follow-up (55.35 (s.d. = 18.28) and 54.16 (s.d. = 18.41), respectively). Cost-effectiveness planes based on non-parametric bootstrapping showed that OPUS was less costly and more effective in 70% of the replications. For a willingness-to-pay up to €50,000 the probability that OPUS was cost-effective was more than 80%. CONCLUSIONS The incremental cost-effectiveness analysis showed that there was a high probability of OPUS being cost-effective compared with standard treatment.

Health care costs, work productivity and activity impairment in non-malignant chronic pain patients

This study explores the costs of non-malignant chronic pain in patients awaiting treatment in a multidisciplinary pain clinic in a hospital setting. Health care costs due to chronic pain are particular high during the first year after pain onset, and remain high compared with health care costs before pain onset. The majority of chronic pain patients incur the costs of alternative treatments. Chronic pain causes production losses at work, as well as impairment of non-work activities.

Quality of life in rhinoconjunctivitis assessed with generic and disease specific questionnaires

Background:  Illness as perceived by the allergic patient with asthma and/or rhinoconjunctivitis (RC) can be assessed by measurements of their health‐related quality of life (HRQL). For this purpose the RC Quality of Life Questionnaire (RQLQ) has gained general acceptance; however, as most allergic patients experience symptoms from multiple organs, disease‐specific HRQL measures may be deficient. This study compares a generic and a disease‐specific HRQL instrument in grass and/or mite‐allergic patients.

Cost-effectiveness estimate of prehospital thrombolysis Results of the PHANTOM-S Study

Objective: To analyze the cost-effectiveness of shorter delays to treatment and increased thrombolysis rate as shown in the PHANTOM-S (Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke) Study. Methods: In addition to intermediate outcomes (time to thrombolysis) and treatment rates, we registered all resource consequences of the intervention. The analyzed treatment effects of the intervention were restricted to distribution of IV thrombolysis (IVT) administrations according to time intervals. Intermediate outcomes were extrapolated to final outcomes according to numbers needed to treat derived from pooled IVT trials and translated to gains in quality-adjusted life-years (QALYs). Results: The net annual cost of the Stroke Emergency Mobile (STEMO) prehospital stroke concept was €963,954. The higher frequency of IVT administrations per year (310 vs 225) and higher proportions of patients treated in the early time interval (within 90 minutes: 48.1% vs 37.4%; 91–180 minutes: 37.4% vs 50%; 181–270 minutes: 14.5% vs 12.8%) resulted in an annual expected health gain of avoidance of 18 cases of disability equaling 29.7 QALYs. This produced an incremental cost-effectiveness ratio of €32,456 per QALY. Conclusions: Depending on willingness-to-pay thresholds in societal perspectives, the STEMO prehospital stroke concept has the potential of providing a reasonable innovation even in health-economic dimensions.

Home-based video exercise intervention for community-dwelling frail older women: a randomized controlled trial

Background and aims: Home-based exercise is a viable solution for frail elderly individuals with difficulties in reaching exercise facilities outside home. The aim of this study was to determine the effects of a home-based video exercise program on physiological performance, functional capacity and health-related quality of life. Methods: Community-dwelling frail women ≥75 yrs, receiving public home care, were randomized into a training group (n=30) and a control group (n=31). Participants exercised for 26 minutes, three times per week for five months. Both groups received a bi-weekly telephone call. The effect of intervention was evaluated by the physical performance test, mobility-tiredness score, maximal isometric handgrip and biceps strength, lower limb explosive power, repeated chair rise (5 times), 10-m maximal walking-speed, semi-tandem balance, and health-related quality of life, as measured by EQ-5D and self-rated health. Results: Twenty-five participants (83%) in the training group and 28 (90%) in the control group completed the project. Adherence to the training protocol was on average 89.2%. At follow-up, between-group analysis revealed a significant difference only in EQ-5D (valued by time-trade-off tariffs), resulting from a significant decrease observed in the control group and a trend towards an increase in the training group (p=0.082). Significant within-group improvements, ranging from 8–35%, were also observed for the physical performance test, mobility-tiredness score, handgrip, biceps strength, chair rise, and 10-m maximal walking-speed in the training group, and for walking-speed and self-rated health in the control group. Conclusions: These results suggest that home-based training for frail older women using an exercise video induces lasting health-related quality-of-life (EQ-5D). In addition, a tendency towards improvements in physiological performance and functional capacity was observed.

Patient related outcomes in a real life prospective follow up study: Allergen immunotherapy increase quality of life and reduce sick days

BackgroundOne fourth of the adult population in Europe suffer from respiratory allergy. Subcutaneous-allergen-specific-immunotherapy (SCIT) has long-term disease modifying effect on disease specific Health-Related Quality of Life (HRQoL). The purpose of this study was to assess the effect of SCIT on alternative disease outcomes in patients with grass-pollen and/or house dust mite induced allergic rhino-conjunctivitis and/or an asthma diagnosis. Focus was on expressing outcomes in terms of generic quality of life (Quality-Adjusted-Life-Years (QALY)) and reductions in sick days.MethodsThe study was a multi-centre study with prospective follow-up. 248 patients were initiated on SCIT. The disease specific Rhino-conjunctivitis Quality of Life Questionnaire (RQLQ) and two generic (HRQoL) instruments 15D and EQ-5D were used at baseline and at follow-up. The outcome measures included change in; disease severity, RQLQ-scores, number of days with symptoms- and number of sick days per year and finally changes in generic HRQoL and thus, QALY. Disease severity was assessed by specialist doctors; severity of rhino-conjunctivitis was classified according to the Allergic Rhinitis and its Impact on Asthma (ARIA) and asthma severity according to the Global Initiative for Asthma (GINA guideline). The remaining outcome measures were assessed by the patients in questionnaires at baseline and at follow-up. An intension to treat approach was applied. For missing items imputation of sample mean base-line values or follow-up values were used after specified criteria. The effect of SCIT on rhino-conjunctivitis and/or asthma diagnoses was analysed at follow-up using three logistic regression models.ResultsThe disease severity showed significantly improved disease control. Mean RQLQ-score was reduced from 3.02 at baseline to 2.00 at follow-up. Average annual days with symptoms were reduced from 189 to 145 days whilst annual sick days were reduced from 3.7 to 1.2 days. The 15D-score increased from 0.83 to 0.86 and the EQ-5D-score from 0.70 to 0.77, which indicated an annual gain per patient of 0.03-0.06 QALY.ConclusionsAllergic patients suffering from rhino-conjunctivitis alone or rhino-conjunctivitis and asthma experience significantly increased HRQoL and they gain 0.03-0.06 QALY, when treated with SCIT for one year.Trial registrationThe study was registered at ClinicalTrials.gov with the identifier:NCT01486498.

Atrial fibrillation detected by continuous electrocardiographic monitoring using implantable loop recorder to prevent stroke in individuals at risk (the LOOP study): Rationale and design of a large randomized controlled trial

Background Atrial fibrillation (AF) increases the rate of stroke 5‐fold, and AF‐related strokes have a poorer prognosis compared with non–AF‐related strokes. Atrial fibrillation and stroke constitute an intensifying challenge, and health care organizations are calling for awareness on the topic. Previous studies have demonstrated that AF is often asymptomatic and consequently undiagnosed. The implantable loop recorder (ILR) allows for continuous, long‐term electrocardiographic monitoring with daily transmission of arrhythmia information, potentially leading to improvement in AF detection and stroke prevention. Methods The LOOP study is an investigator‐initiated, randomized controlled trial with 6,000 participants randomized 3:1 to a control group or to receive an ILR with continuous electrocardiographic monitoring. Participants are identified from Danish registries and are eligible for inclusion if 70 years or older and previously diagnosed as having at least one of the following conditions: hypertension, diabetes mellitus, heart failure, or previous stroke. Exclusion criteria include history of AF and current oral anticoagulation treatment. When an AF episode lasting ≥6 minutes is detected, oral anticoagulation will be initiated according to guidelines. Expected follow‐up is 4 years. The primary end point is time to stroke or systemic embolism, whereas secondary end points include time to AF diagnosis and death. Conclusion The LOOP study will evaluate health benefits and cost‐effectiveness of ILR as a screening tool for AF to prevent stroke in patients at risk. Secondary objectives include identification of risk factors for the development of AF and characterization of arrhythmias in the population. The trial holds the potential to influence the future of stroke prevention.

Characteristics of patients receiving allergy vaccination: to which extent do socio-economic factors play a role?

Background: Little is known about characteristics of patients receiving allergen-specific immunotherapy. Identifying obstacles to appropriate treatment according to guidelines may facilitate the development of strategies aiming at improved treatment of patients with allergic respiratory diseases. The objective of this study was to investigate differences in disease severity, demographic and socioeconomic status between allergic rhinitis patients receiving allergen-specific immunotherapy and allergic rhinitis patients not receiving allergen-specific immunotherapy. Methods: A total of 366 patients were studied of whom 210 were going to receive subcutaneously administrated immunotherapy (SIT) against grass pollen and/or house dust mite allergy. The severity of rhino-conjunctivitis (hay fever) and/or asthma was classified according to international guidelines. The questionnaires included an EQ-5D visual analogue scale instrument and some socio-economic questions. Results: Severity of disease, young age, high level of education as well as greater perceived impairment of health-related quality of life due to allergic symptoms were significantly associated with use of SIT. Somewhat unexpectedly, household income was not associated with use of SIT. Conclusion: Use of SIT was associated with both disease severity measures and educational level, but not income level. These results suggest social inequality as reflected by lower use of SIT among patients with lower educational level may represent an obstacle to treatment with SIT.

Willingness to pay for allergy-vaccination among Danish patients with respiratory allergy

OBJECTIVE The aim of this study was to elicit willingness to pay (WTP) for allergen-specific subcutaneous injection immunotherapy (SCIT) in a cohort of respondents suffering from allergic-rhinoconjunctivitis (a-RC)/asthma, and to investigate how patients self-select to SCIT according to need. METHODS A random sample of the general population was screened for a-RC/asthma and asked if they were willing to consider SCIT. They were asked to state their WTP for SCIT by way of a discrete choice question (DC-q), an open-ended WTP question (o-WTP-q), and questions relating to their sociodemographic background and the severity of their a-RC/asthma. The characteristics of respondents demanding SCIT were compared with the characteristics of respondents who have actually received SCIT to establish possible barriers to demand. RESULTS Our results suggest that respondents do well in self-selecting themselves to SCIT on the basis of need according to disease burden measured in terms of a-RC classification, number of contacts with a general practitioner, number of sick days, and potential quality-adjusted life-year loss. Mean WTP for SCIT was estimated at 655 euros (median, 267 euros) (o-WTP-q) and 903 euros (95 percent confidence limit, 348-1,459) (DC-q). CONCLUSION Characteristics of respondents, who consider SCIT and are willing to pay for SCIT, suggest that allergy sufferers select themselves appropriately according to need and not according to other characteristics, such as income or education. There is a significant discrepancy between those who hypothetically consider SCIT and those demanding SCIT in real life. This study suggests that there are barriers to entry related to age and education, but not to income.