Education, employment, and income among people living with cystic fibrosis across three decades - A matched cohort study using Danish health registries.

BACKGROUND: Past and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population. METHODS: This nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality. RESULTS: The Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts. CONCLUSIONS: The disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life.

100-mJ, 100-W cryogenically cooled Yb:YLF laser.

We present a diode-pumped Yb:YLF laser system generating 100-mJ sub-ps pulses at a 1-kHz repetition rate (100 W average power) by chirped-pulse amplification. The laser consists of a cryogenically cooled 78 K, regenerative, eight-pass booster amplifier seeded by an all-fiber front end. The output pulses are compressed to 980 fs in a single-grating Treacy compressor with a throughput of 89%. The laser will be applied to multi-cycle THz generation and pumping of high average power parametric amplifiers.

Broadly tunable (993-1110 nm) Yb:YLF laser.

We have investigated room-temperature continuous-wave (cw) lasing performance of Yb:YLF oscillators in detail using rod-type crystals with low Yb-doping (2%). The laser is pumped by a low-cost, high brightness, 10 W, 960 nm single-emitter multimode diode. Laser performance is acquired in both E//a and E//c configurations, using 12 different output couplers with transmission ranging from 0.015% to 70%. We have estimated the passive loss of the Yb:YLF crystal as 0.06% per cm, corresponding to an impressive crystal figure of merit above 4000. The low-doping level not only reduces the system losses but also minimizes the thermal load as the low doped crystals enable distribution of heat load in a greater volume. Using the advantages of lower loss and improved thermal behavior, we have achieved cw output power above 4 W, cw slope efficiencies up to 78%, and a record cw tuning range covering the 993-1110 nm region (117 nm). The output power performance achieved in this initial work is limited by the available pump power, and future room-temperature Yb:YLF systems have the potential to produce higher output power levels.

Semiconductor saturable absorber mirror mode-locked Yb:YLF laser with pulses of 40 fs.

We have generated pulses as short as 40 fs with an average power of 265 mW from a semiconductor saturable absorber mirror (SESAM) mode-locked Yb:YLF oscillator employing a 1% transmitting output coupler (OC). The room-temperature laser is pumped by a low-cost 960 nm single-emitter multimode diode and dispersion compensation is provided via double chirped mirrors (DCMs). The 40-fs pulses are centered around 1050 nm with a width of 34 nm at a repetition rate of 87.3 MHz. By increasing the output coupling to 5% and by using Gires-Tournois interferometer (GTI) mirrors for dispersion compensation, we have also demonstrated 380-fs pulses with 1.85 W of average power around 1025 nm at a repetition rate of 190.4 MHz. Using an intracavity off-surface optic axis birefringent filter, the central wavelength of the pulses could be tuned in the 1020-1025 nm and 1019-1047 nm ranges for the 5% and 1% transmitting OCs, respectively. To the best of our knowledge, these are the shortest pulses and highest average and peak powers generated from room-temperature Yb:YLF lasers to date.

Positron emission tomography-computed tomography (PET-CT) in suspected malignant pleural effusion. An updated systematic review and meta-analysis.

The role of PET and integrated PET-CT in the diagnostic workup of suspected malignant pleural effusions is unknown. Earlier systematic reviews (published 2014 and 2015) both included pleural pathology without effusion, and reached contradictory conclusions. Five studies have been published since the latest review. This systematic review and meta-analysis aims to summarise the evidence of PET and integrated PET-CT in predicting pleural malignancy in patients suspected of having malignant pleural effusions. A meta-analysis based on a systematic literature search in Cochrane Library, Medline, EMBASE and Clinicaltrials.gov was performed. Diagnostic studies evaluating the performance of PET or PET-CT in patients with suspected malignant pleural effusion, using pleural fluid cytology or histopathology as the reference test, and presenting sufficient data for constructing a 2x2 table were included. The quality of the studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 score. Subgroup analyses on image modality, interpretation method and known malignancy status pre index-test application were planned. Seven studies with low risk of bias were included. The pooled ability to separate benign from malignant effusions varied with image modality, interpretation method and known malignancy status pre index-test application. In studies using PET-CT, visual/qualitative image analysis was superior to semi-quantitative with positive (LR + ) and negative likelihood ratio (LR-) of 9.9 (4.5-15.3) respectively 0.1 (0.1-0.2). There was considerable heterogeneity among studies. In conclusion, visual/qualitative image analysis of integrated PET-CT seems to add relevant information in the work-up of suspected malignant pleural effusions with LR + and LR- close to rigorous pre-set cut-offs of > 10 and < 0.1. However, the quality of evidence was low due to inter-study heterogeneity, and inability to assess meta-bias. Clinical Trial Registration: The protocol was uploaded to the PROSPERO database (CRD42020213319) on the 13th of October 2020.

Mode-locked Cr:LiSAF laser far off the gain peak: tunable sub-200-fs pulses near 1 µm.

We report, to the best of our knowledge, the first mode-locking results of a Cr:LiSAF laser near the 1 µm region. The system is pumped only by a single 1.1 W high-brightness tapered diode laser at 675 nm. A semiconductor saturable absorber mirror (SESAM) with a modulation depth of 1.5% and non-saturable losses below 0.5% was used for mode-locking. Once mode-locked, the Cr:LiSAF laser produced almost-transform-limited sub-200-fs pulses with up to 12.5 mW of average power at a repetition rate of 150 MHz. Using an intracavity birefringent filter, the central wavelength of the pulses could be smoothly tuned in the 1000-1020 nm range. Via careful dispersion optimization, pulse widths could be reduced down to the 110-fs level. The performance in this initial study was limited by the design parameters of the SESAM used, especially its passive losses and could be improved with an optimized SESAM design.

Highly efficient cryogenic Yb:YLF regenerative amplifier with 250 W average power.

We report an efficient diode-pumped high-power cryogenic regenerative amplifier operating at 1019 nm employing the c axis of Yb:YLF. Compared to the usually selected 1017 nm transition of the a axis, the c-axis 1019 nm line has a three-fold higher emission cross section and still possesses a full-width at half-maximum (FWHM) of 6.5 nm at 125 K. The chirped-pulse amplifier system is seeded by a fiber front-end with energy of 30 nJ and a stretched pulse width of 2 ns. In regenerative amplification studies, using the advantage of higher gain in the c axis, we have achieved record average powers up to 370 W with an extraction efficiency of 78% at a 50 kHz repetition rate. The output pulses were centered on 1019.15 nm with a FWHM bandwidth of 1.25 nm, which supports sub-1.5 ps pulse durations. The output beam maintained a TEM00 beam profile at output power levels below 250 W with an M2 below 1.2. Above this power level, the thermally induced lensing in Yb:YLF created a multimode output beam. The thermal lens was rather dynamic and deteriorated the system stability above a 250 W average power level.

High power (>500W) cryogenically cooled Yb:YLF cw-oscillator operating at 995†nm and 1019†nm using E//c axis for lasing.

We present record continuous wave (cw) output power levels from cryogenically cooled Yb:YLiF4 (Yb:YLF) lasers in rod geometry. The laser system is pumped by a state-of-the-art 960 nm diode module, and vertically polarized lasing was employed using the E//c axis of Yb:YLF. Lasing performance was investigated at different output coupling levels in different cavity configurations and the laser crystal temperature was estimated via monitoring the emission spectrum of the gain media. We have obtained a cw output power up to 400 W at a wavelength of 995 nm. The absorbed pump power was around 720 W, and the laser output had a TEM00 beam profile with an M2 of 1.3 in both axes. At higher absorbed pump power levels with increasing laser crystal temperature, we observed a lasing wavelength shift from 995 nm to 1019 nm. In this regime cw output power levels above 500 W have been achieved at an absorbed pump power of 750 W. Further power scaling was limited by the onset of strong thermal lensing. We discuss underlying physical mechanisms for the wavelength shift and present detailed temperature measurements under lasing conditions.

Computed tomography of the chest in unilateral pleural effusions: outcome of the British Thoracic Society guideline.

BACKGROUND: The guidelines from the British Thoracic Society (BTS) regarding the investigation of unilateral pleural effusions recommend computed tomography (CT) in exudates. We decided to investigate if clinicians follow BTS guidelines' recommendations with respect to CT in patients with unilateral pleural effusions. Secondly, to investigate the diagnostic consequences of following and not following this recommendation. METHODS: The study was a retrospective, non-randomized study including consecutive patients referred to our tertiary centers in 2013-2016 because of unilateral pleural effusion. Patients undergoing chest CT for unilateral pleural effusion of unknown cause after thoracentesis and chest X-ray were included. Patients were categorized as having pleural exudates or transudates, according to Light's criteria, if applicable. We registered use of CT, and calculated diagnostic values. RESULTS: In total, 323 of the 465 included patients underwent CT (69%). CT was performed in the majority of patients not having an exudate (transudates: n=40; 54%; Light's criteria not assessed: n=111; 67%). 18F-FDG positron emission tomography (PET)/CT without prior CT was performed in 32 patients with an exudate (58%). The sensitivity of a non-guideline supported CT (70%) was significantly higher compared to a guideline supported CT (47%), P value <0.045. The post-test probability of a positive guideline-supported CT [likelihood ratio (LR) positive 3.26] for a later diagnosis of thoracic malignancy increased the probability from 25% to 52%. A negative CT (LR negative 0.62) decreased the probability to 17%. For a non-guideline-supported CT the numbers were (LR positive 3.42) 53% and (LR negative 0.38) 11%, respectively. CONCLUSIONS: Clinicians appear not to follow BTS guidelines when deciding to perform chest CT. The relevance of this deviation is supported by the superior sensitivity of CT non-guideline supported CT. Overall, CT is associated with suboptimal sensitivity and negative predictive values for the diagnosis of thoracic malignancy.

Incidence of malignancy and survival in patients with idiopathic pleuritis.

BACKGROUND: The long-term outcome after non-diagnostic thoracoscopy (idiopathic pleuritis) has not been investigated in nationwide studies, and the survival has never been estimated. Therefore, we decided to investigate the three-year incidence of malignancy and survival of patients with idiopathic pleuritis. METHODS: Retrospective, register-based, nationwide study of patients undergoing diagnostic video-assisted thoracoscopic surgery (VATS) thoracoscopy ≤30 days after thoracentesis, using The National Patient Registry and The Danish Cancer Registry. Idiopathic pleuritis was defined as; no diagnosis of malignancy within 31 days after VATS. Patients were followed for 36 months after VATS. RESULTS: In total, idiopathic pleuritis were identified in 547 out of 658 patients undergoing VATS (83%), and 29 (5%) were diagnosed with malignancy during the 3 years follow-up period after VATS. Of these, 93% were diagnosed with malignancy within the first year. Numbers-needed-to-follow-up for detecting one case of malignancy was 18 during the first year after VATS and 250 in the two subsequent years. Survival was independent on type of malignancy (MPM vs. other malignancies; P=0.13) and of time from VATS to diagnosis (≤31 days vs. 1-36 months; P=0.15). Median survival in the non-malignant group was 1,095 days. CONCLUSIONS: Our study confirms a low incidence of malignancy in idiopathic pleuritis after VATS. Nearly all incident cases of malignancy were diagnosed within 12 months from VATS. No survival disadvantage was observed in patients with incident malignancy. Our data suggest that follow-up of idiopathic pleuritis could safely be limited to 1 year. The optimal follow-up strategy remains to be investigated.

The value of computed tomography in discriminating malignant from non-malignant causes of unresolved unilateral pleural effusions: a systematic review.

The scientific background in expert-opinion papers for recommending Computed Tomography (CT) in unilateral pleural exudates is based on studies including patients with other findings than unilateral pleural effusions or selected patients undergoing thoracoscopy. Therefore, we performed a systematic review investigating the sensitivity of CT for predicting malignancy in patients with unilateral, non-transudative, pleural effusions. A search strategy was developed with the assistance of a medical information specialist at our university library. We searched PubMed/MEDLINE, EMBASE and Cochrane Library, ClinicalTrials.gov and articles citing the included studies. No date restrictions were applied (the first included paper was published in 2001 (1)), and only literature in English was included. We used the Quality Assessment of Diagnostic Accuracy Studies 2 for bias assessment. We registered the protocol at PROSPERO (CRD42018094830). Five studies were included, two prospective and three retrospective, all performed in Western Europe. No study reported diagnostic values for patients with unilateral, non-transudative pleural effusions only; one study did for unilateral pleural effusions. In the remaining studies, most patients had unilateral effusions and non-transudative effusions. Patients were primarily males and >70 years. All but one study found a high incidence of malignancy, dominated by malignant pleural mesothelioma. All studies were limited by risk of bias and applicability, predominantly regarding study population, pretests and index test. The current evidence supporting the sensitivity of CT for predicting malignancy in unilateral pleural effusions (both non-transudative and all types of effusion) is very low and did not allow meta-analysis. Standardization of patient population and CT protocol may facilitate conclusions of futures studies.

Diagnostic property of direct referral from general practitioners to contrast-enhanced thoracoabdominal CT in patients with serious but non-specific symptoms or signs of cancer: a retrospective cohort study on cancer prevalence after 12 months.

OBJECTIVES: To describe the diagnostic properties of thoracoabdominal contrast-enhanced CT (ceCT), when general practitioners (GPs) managed referral to ceCT through the non-specific symptoms or signs of cancer-cancer patient pathway (NSSC-CPP). DESIGN: Retrospective cohort study including patients from a part of Denmark. SETTING: Department of Internal Medicine at a university hospital. PARTICIPANTS: In total, 529 patients underwent ceCT. PRIMARY AND SECONDARY OUTCOMES: Our primary objective was to estimate the negative and positive likelihood ratios for being diagnosed with cancer within 1 year after ceCT. Our secondary outcomes were prevalence and final diagnoses of malignancy (including temporal trends since implementation of NSSC-CPP in 2012), the prevalence of revision of CT scans and referral patterns based on ceCT results. RESULTS: In total, 529 subjects underwent ceCT and malignancy was identified in 104 (19.7%) patients; 101 (97.1%) during initial workup and 3 patients during the subsequent 12 months follow-up.Eleven patients had a false-negative ceCT, and revision classified the ceCT as 'probable/possible malignancy' in eight (73%) patients. The negative predictive value was 98% and positive predictive value 63%. Negative and positive likelihood ratios for malignancy was 0.1 and 7.9, respectively. CONCLUSION: Our study shows that ceCT as part of GP-coordinated workup has a low negative likelihood ratio for identifying malignancy; this is important since identifying patients for further workup is vital.

Serum YKL-40 for monitoring myocardial ischemia after revascularization in patients with stable coronary artery disease.

AIM: The aim was to investigate the inflammatory biomarker YKL-40 as a monitor of myocardial ischemia in patients with coronary artery disease (CAD). METHODS: A total of 311 patients with stable CAD were included. Blood samples were taken at baseline, the day after coronary angiography and/or after percutaneous coronary intervention and after 6 months. RESULTS: A total of 148 (48%) patients were revascularized and 163 patients underwent only coronary angiography. In the entire population, serum YKL-40 increased significantly from baseline to 6 months (p = 0.05). This tendency was seen in nonrevascularized patients (p = 0.06), but not in revascularized patients (p = 0.46). Serum YKL-40 increased approximately 25% the day after the invasive procedure (p < 0.001) and then decreased significantly to nearly baseline after 6 months (p = 0.002). CONCLUSION: Serum YKL-40 is a potential promising biomarker of disease progression but not of myocardial ischemia in patients with stable CAD.

The influence of contrast media on kidney function in patients with stable coronary artery disease.

AIMS: To investigate the incidence of contrast media-induced nephropathy (CIN) in patients with stable coronary artery disease (CAD) referred for elective coronary intervention following hydration routines. The reversibility of CIN was followed in a 6 month-period. METHODS AND RESULTS: A total of 447 patients referred for elective coronary intervention due to suspected CAD were included. Blood samples were collected before and 24 h after intervention and medical records were obtained. Patients had no drinking fluid restrictions and were routinely treated with a 1000 ml saline infusion. All patients were invited to a 6-month examination and collection of blood samples. RESULTS: A total of 19 patients (4.3%) developed CIN. CIN patients had a pre-investigation higher estimated glomerular filtration rate (eGRF), lower level of kidney failure and lower creatinine level than non-CIN patients. Kidney function was not normalized in CIN patients 6 months after the intervention. Two patients still met the definition of CIN. CONCLUSION: With no restriction in fluid intake and supplementary infusion of saline, only a few patients with stable CAD developed early indications of CIN during elective coronary interventions. Kidney function and the amount of contrast media used was not a predictor of CIN development. The induced CIN was not completely normalized in a 6-month follow-up period.