IN.PACT AV access randomized trial: Japan cohort outcomes through 12 months

Purpose

There is a lack of adjudicated and prospectively randomized published outcomes on the use of drug-coated balloons (DCB) to treat dysfunctional arteriovenous fistula in Asian patients. This post hoc subgroup analysis of 112 Japanese participants from the global IN.PACT AV Access trial reports outcomes through 12 months.

Materials and Methods

Participants were treated with DCB (n = 58) or standard non-coated percutaneous transluminal angioplasty (PTA) balloons (n = 54). Outcomes included target lesion primary patency (TLPP), access circuit primary patency, and safety.

Results

Through 6 months, TLPP was 86.0% (49/57) in the DCB group and 49.1% (26/53) in the PTA group (p < 0.001). Through 12 months, TLPP was 67.3% (37/55) in the DCB group and 43.4% (23/53) in the PTA group (p = 0.013).

Conclusion

In this post hoc analysis of Japanese participants from the IN.PACT AV Access trial, participants treated with DCB had higher TLPP through 6 and 12 months compared with PTA.     

Subtypes of cognitive impairment in depressed older adults.

The authors examined the cognitive profiles of 104 older adults with major depression and empirically identified three subgroups with distinct patterns of cognitive impairment. The entire sample demonstrated memory impairment relative to age-standardized scores, distributed equally across the three cognitive subgroups. One-third of subjects displayed either executive impairment or attentional deficits. The subgroup with executive dysfunction had greater behavioral disability. Identification of executive impairment in depressed older adults may facilitate intervention for disturbances in planning, sequencing, organizing, and abstracting. Demonstrating the presence of subtypes of cognitive impairments in older adults may provide the basis for further investigation of mechanisms of late-life depression and the pathophysiology of antidepressant response. The association of behavioral disability with executive dysfunction can initiate an inquiry into the biology of functional impairment ultimately linking biological research to studies of treatment effectiveness.     

Second-line paclitaxel in non-small cell lung cancer initially treated with cisplatin: a study by the European Lung Cancer Working Party

In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08-2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08-2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26-2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy.     

Flow and particle deposition in the Turbuhaler: A CFD simulation

In this work the steady-state flow in a commercial dry powder inhaler device, DPI (i.e., Turbuhaler) is described using computational fluid dynamics. The Navier–Stokes equations are solved using commercial CFD software considering different flow models, i.e., laminar, k–ε, k–ε RNG, and k–ω SST as well as large Eddy simulation. Particle motion and deposition are described using a Eulerian-fluid/Lagrangian-particle approach. Particle collisions with the DPI walls are taken to result in deposition when the normal collision velocity is less than a critical capture velocity. Flow and particle deposition, for a range of mouthpiece pressure drops (i.e., 800–8800 Pa), as well as particle sizes corresponding to single particles and aggregates (i.e., 0.5–20 μm), are examined. The total volumetric outflow rate, the overall particle deposition as well as the spatial distribution of deposition sites in the DPI are determined. The transitional k–ω SST model for turbulent flow was found to produce results most similar to a reference solution obtained with LES, as well as experimental results for the pressure drop in the DPI. Overall, the simulation results are found to be in agreement with the available experimental data for local and total particle deposition.     

Saw-tooth cardiomyopathy

We report a rare case of a quinticuspid aortic valve associated with regurgitation and dilation of the ascending aorta, which was diagnosed and post-surgically followed up by cardiovascular magnetic resonance and dual source computed tomography.     

Late-life depression: a model for medical classification.

Geriatric psychiatric syndromes might serve as the starting point for a medical classification of psychiatric disorders, because their medical and neurological comorbidity and their clinical, neuropsychological, and neuroimaging features often reflect specific brain abnormalities. Geriatric syndromes, however, consist of complex behaviors that are unlikely to be caused by single lesions. We propose a model in which aging-related changes in specific brain structures increase the propensity for the development of certain psychiatric syndromes. The predisposing factors are distinct from the mechanisms mediating the expression of a syndromic state, much like hypertension is distinct from stroke, but constitutes a morbid vulnerability. We argue that research seeking to identify both brain abnormalities conferring vulnerability as well as the mediating mechanisms of symptomatology has the potential to lead to a medical classification of psychiatric disorders. In addition, a medical classification can guide the effort to improve treatment and prevention of psychiatric disorders as it can direct therapeutic efforts to the underlying predisposing abnormalities, the syndrome-mediating mechanisms, and to development of behavioral skills needed for coping with adversity and disability.     

Plasma exchange (PE) treatment in drug-induced toxic epidermal necrolysis (TEN).

Toxic epidermal necrolysis (TEN) or Lyell's syndrome is a rare fulminating skin disease notorious for its rapidly progressive course and high mortality rate. TEN is characterized by the sudden onset of epithelial necrosis of skin with frequently associated involvement of the gastrointestinal, genitourinary tract and bronchopulmonary linings. We describe the clinical course of five patients with severe drug-induced TEN, treated with PE. The suspected drugs were carbamazepine in one patient, paracetamol in one, a combination of paracetamol and mefenamic acid in one, allopurinol in one and ciprofloxacin in one. Three had a skin involvement affecting almost the entire surface of the body. In addition to the skin lesions, mouth, esophagus and lungs were also involved. Steroids proved ineffective. PE was carried out because of the rapid deterioration of the clinical picture. The mean number of PE sessions was 3.22 (range 1-5). Complete remission of the syndrome was achieved in four patients. One patient died due to septic shock. As so far there is no treatment of proven value for this condition, controlled trials should be set up in order to assess the value of PE in TEN.     

Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression.

BACKGROUND: Plasma activity of dopamine beta-hydroxylase (DbetaH), the enzyme that converts dopamine to norepinephrine, is reportedly lower in patients with unipolar major depression with psychotic features (UDPF) than in those with nonpsychotic unipolar major depression (UD). Plasma DbetaH is under genetic control by the structural locus encoding DbetaH protein, DBH. This study tested the hypothesis that diagnosis-specific allelic variation at DBH accounts for lower plasma DbetaH in UDPF. METHODS: Plasma DbetaH activity was measured in samples from patients with UDPF (n = 33) and UD (n = 45). Genotypes were determined at several functional DBH polymorphisms, including C-1021T, a single nucleotide polymorphism (SNP) in the proximal 5' region that associates with variation in plasma DbetaH activity. RESULTS: Mean plasma DbetaH activity was significantly lower in UDPF than in UD. Genotyping at DBH did not reveal genetic associations distinguishing UDPF from UD. A two-way analysis of variance showed significant effects of genotype and diagnostic group but no significant interaction. CONCLUSIONS: Although the effects of the diagnosis of UDPF, and of DBH allele status, on plasma DbetaH activity were replicated, the lower plasma DbetaH in patients with UDPF was not accounted for by DBH genotype. Several explanations for this result are possible. First, other variants at DBH, or at other loci, could account for the findings. Second, nongenetic factors could account for the differences in plasma DbetaH. In this regard, we hypothesize that abnormal regulation of hypothalamic-pituitary-adrenal function in UDPF lowers expression of DbetaH protein, which could in turn alter the ratio of dopamine and norepinephrine in noradrenergic neurons, thereby promoting development of psychotic symptoms.