Frequency dependency of temporal contrast adaptation in normal subjects

AbstractThe aim of this study was to determine the influence of temporal frequency of temporal contrast adaptation on contrast sensitivity in healthy subjects. Temporal contrast sensitivities (TCS) were measured monocularly in seven healthy subjects with a modified ERG full-field bowl stimulator at eight different test temporal frequencies (9, 15, 20, 25, 31, 37, 44, 51Hz) using a two-alternative-forced-choice strategy. Before each presentation of the test stimulus, a 100% contrast adapting flicker stimulus was presented (frequencies: 9, 15, 20, 25, 31, 37, 44, 51, 100Hz). At each adapting frequency, a complete set of TCSs was measured. All temporal contrast sensitivities decreased with increasing temporal frequencies. Adaptation led to a general temporal contrast sensitivity decrease. Largest adaptation effects were seen at an adaptation frequency of 25Hz. Reduction of contrast sensitivity was significantly larger at 25Hz adaptation than at 9Hz adaptation (t-test of paired samples, Bonferroni corrected). The results of this study showed a general TCS decrease with the largest effect at an adaptation frequency of 25Hz. This finding indicates that the contrast adaptation probably occurred in the magnocellular-pathway. In future clinical studies adaptation effects could be investigated in patients with reduced temporal contrast sensitivity

Temporal contrast sensitivity: A potential parameter for glaucoma progression, especially in advanced stages

INTRODUCTION. Previously it could be shown that temporal contrast sensitivity is affected by glaucoma and maximally influenced after 25-Hz adaptation in normals. This study investigated different kinds of 25-Hz temporal contrast adaptation on TCS in patients with ocular hypertension, preperimetric primary open-angle glaucoma, and perimetric open-angle glaucoma. Additionally, correlations of measured data with parameters of glaucoma diagnostic were done and assessed for the potential use of TCS as a parameter for glaucoma progression. MATERIALS AND METHODS. One hundred and four subjects were included: 44 normals, 14 ocular hypertensions, 11 preperimetric primary open-angle glaucomas, and 35 perimetric open-angle glaucomas. Using the Erlangen Flicker Test, temporal contrast sensitivity was measured without adaptation, after pre-adaptation and after pre- and re-adaptations at 25 Hz. Reliability analyses were done. RESULTS. All test strategies showed high reliability (a-Cronbach’s > 0.86). In normals, age-dependency of temporal contrast sensitivity without adaptation (p = 0.052) and after pre- and re-adaptation (p = 0.008) was observed. Temporal contrast sensitivity is significantly reduced after pre-adaptation for all subjects (p < 0.001). Reduction of temporal contrast sensitivity after pre- and re-adaptations was significant in all groups (p < 0.001), but it was smaller than after single pre-adaptation (p < 0.001). Temporal contrast sensitivity without adaptation was significantly reduced in patients with perimetric glaucoma (p = 0.040) but not in patients with ocular hypertension and preperimetric glaucoma. Correlation analyses yielded a significant correlation between temporal contrast sensitivity without adaptation and mean defect (p = 0.003, r = –0.329), loss variance (p = 0.027, r = –0.256), and retinal nerve fibre layer thickness (p < 0.001, r = 0.413) for all subjects and between temporal contrast sensitivity after pre-adaptation and mean defect (p = 0.045, r = –0.239). CONCLUSIONS. Temporal contrast sensitivity seems to be affected in perimetric glaucoma with an overall reduction after adaptation. Significant correlations of temporal contrast sensitivity with perimetric and morphologic parameters offer new aspects of its potential use as a glaucoma progressions marker, especially in advanced stages when perimetric diagnosis is limited

Endovascular repair of an actively hemorrhaging gunshot injury to the abdominal aorta

Endovascular stents have had a limited role in the management of trauma and vascular emergencies involving active hemorrhage. We describe a patient with delayed rupture of the infrarenal aorta after intra-abdominal sepsis caused the breakdown of a primary aortic repair. A stent-graft repair was performed, as concomitant injuries did not allow anterior access to the aorta. This report describes the successful endovascular repair of an actively hemorrhaging penetrating abdominal aortic injury. Endovascular approaches to aortic injuries may be valuable in settings where a hostile abdomen precludes traditional open repair

Economic evaluation of day hospital versus intensive outpatient mentalization-based treatment alongside a randomized controlled trial with 36-month follow-up

Mentalization-based treatment (MBT) has demonstrated robust effectiveness in the treatment of borderline personality disorder (BPD) in both day hospital (MBT-DH) and intensive outpatient MBT (MBT-IOP) programs. Given the large differences in intensity and associated treatment costs, there is a need for studies comparing their cost-effectiveness. A health economic evaluation of MBT-DH versus MBT-IOP was performed alongside a multicenter randomized controlled trial with a 36-month follow-up. In three mental health-care institutions in the Netherlands, 114 patients were randomly allocated to MBT-DH (n = 70) or MBT-IOP (n = 44) and assessed every 6 months. Societal costs were compared with quality-adjusted life years (QALYs) gained and the number of months in remission over 36 months. The QALY gains over 36 months were 1.96 (SD = 0.58) for MBT-DH and 1.83 (SD = 0.56) for MBT-IOP; the respective number of months in remission were 16.0 (SD = 11.5) and 11.1 (SD = 10.7). Societal costs were €106,038 for MBT-DH and €91,368 for MBT-IOP. The incremental cost for one additional QALY with MBT-DH compared with MBT-IOP was €107,000. The incremental cost for 1 month in remission was almost €3000. Assuming a willingness-to-pay threshold of €50,000 for a QALY, there was a 33% likelihood that MBT-DH is more cost-effective than MBT-IOP in terms of costs per QALY. Although MBT-DH leads to slightly more QALYs and remission months, it is probably not cost-effective when compared with MBT-IOP for BPD patients, as the small additional health benefits in MBT-DH did not outweigh the substantially higher societal costs

Helium ventilation for treatment of post-cardiac arrest syndrome:A safety and feasibility study

AbstractAimBesides supportive care, the only recommended treatment for comatose patients after cardiac arrest is target temperature management. Helium reduces ischaemic injury in animal models, and might ameliorate neurological injury in patients after cardiac arrest. As no studies exist on the use of helium in patients after cardiac arrest we investigated whether this is safe and feasible.MethodsThe study was an open-label single arm intervention study in a mixed-bed academic intensive care unit. We included 25 patients admitted after circulatory arrest, with a presenting rhythm of ventricular fibrillation or pulseless tachycardia, return of spontaneous circulation within 30min and who were treated with hypothermia. Helium was administrated in a 1:1 mix with oxygen for 3h. A safety committee reviewed all ventilation problems, complications and causes of mortality.ResultsHelium ventilation was started 4:59±0:52 (mean±SD)h after circulatory arrest. In one patient, helium ventilation was discontinued prematurely due to oxygenation problems. This was caused by pre-existing pulmonary oedema, and imposed limitations to PEEP and FiO2 by the study protocol, rather than the use of helium ventilation. Sixteen (64%) patients had a favourable neurological outcome.ConclusionsWe found that helium ventilation is feasible and can be used safely in patients treated with hypothermia after cardiac arrest. No adverse events related to the use of helium occurred during the three hours of administration

Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations

BACKGROUND: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population. METHODS: In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of a MET exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy. RESULTS: As of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment. CONCLUSIONS: Among patients with advanced NSCLC with a confirmed MET exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients. Peripheral edema was the main toxic effect of grade 3 or higher. (Funded by Merck [Darmstadt, Germany]; VISION ClinicalTrials.gov number, NCT02864992.)

Mutations in STK11 gene in Czech Peutz-Jeghers patients

<p>Abstract</p> <p>Background</p> <p>Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis. The germline mutations in the serine/threonine kinase 11 (<it>STK11</it>) gene have been shown to be associated with the disease. Individuals with PJS are at increased risk for development of various neoplasms. The aim of the present study was to characterize the genotype and phenotype of Czech patients with PJS.</p> <p>Methods</p> <p>We examined genomic DNA of 8 individuals from five Czech families by sequencing analysis of <it>STK11 </it>gene, covering its promotor region, the entire coding region and the splice-site boundaries, and by multiplex ligation-dependent probe amplification (MLPA) assay designed for the identification of large exonic deletions or duplications of <it>STK11 </it>gene.</p> <p>Results</p> <p>We found pathogenic mutations in <it>STK11 </it>gene in two families fulfilling the diagnostic criteria of PJS and in one of three sporadic cases not complying with the criteria. The patient with the frameshift mutation in <it>STK11 </it>gene developed aggressive gastric cancer. No other studied proband has developed a carcinoma so far.</p> <p>Conclusion</p> <p>Our results showed that a germline mutation of <it>STK11 </it>gene can be found not only in probands fulfilling the PJS diagnostic criteria, but also in some sporadic cases not complying with the criteria. Moreover, we observed a new case of aggressive gastric cancer in a young patient with a frameshift mutation of <it>STK11 </it>gene.</p

Successful and unsuccessful cannabis quitters: Comparing group characteristics and quitting strategies

<p>Abstract</p> <p>Background</p> <p>In order to improve treatments for cannabis use disorder, a better understanding of factors associated with successful quitting is required.</p> <p>Method</p> <p>This study examined differences between successful (<it>n </it>= 87) and unsuccessful (<it>n </it>= 78) cannabis quitters. Participants completed a questionnaire addressing demographic, mental health, and cannabis-related variables, as well as quitting strategies during their most recent quit attempt.</p> <p>Results</p> <p>Eighteen strategies derived from cognitive behavioral therapy were entered into a principal components analysis. The analysis yielded four components, representing (1) Stimulus Removal, (2) Motivation Enhancement, (3) (lack of) Distraction, and (4) (lack of) Coping. Between groups comparisons showed that unsuccessful quitters scored significantly higher on Motivation Enhancement and (lack of) Coping. This may indicate that unsuccessful quitters focus on the desire to quit, but do not sufficiently plan strategies for coping. Unsuccessful quitters also had significantly more symptoms of depression and stress; less education; lower exposure to formal treatment; higher day-to-day exposure to other cannabis users; and higher cannabis dependence scores.</p> <p>Conclusions</p> <p>The findings suggest that coping, environmental modification, and co-morbid mental health problems may be important factors to emphasize in treatments for cannabis use disorder.</p