A cost-effectiveness analysis of prenatal screening strategies for Down syndrome

OBJECTIVE: To evaluate which Down syndrome screening strategy is the most cost-effective. METHODS: Using decision-analysis modeling, we compared the cost-effectiveness of 9 screening strategies for Down syndrome: 1) no screening, 2) first-trimester nuchal translucency (NT) only, 3) first-trimester combined NT and serum screen, 4) first-trimester serum only, 5) quadruple screen, 6) integrated screening, 7) sequential screening, 8) integrated serum only, or 9) maternal age. Costs included cost of tests and resources used for raising a child with Down syndrome. One-way and multiway sensitivity analyses were performed for all model variables. The main outcome measures were cost per Down syndrome case detected, rate of delivering a liveborn neonate with Down syndrome, and rate of diagnostic procedure-related pregnancy loss for each strategy. RESULTS: Sequential screening detected more Down syndrome cases compared with the other strategies, but it had a higher procedure-related loss rate. Integrated serum screening was the most cost-effective strategy. Sensitivity analyses revealed the model to be robust over a wide range of values for the variables. The addition of the cost of genetic sonogram to the second-trimester strategies resulted in first-trimester combined screening becoming the most cost-effective strategy. CONCLUSION: Within our baseline assumptions, integrated serum screening was the most cost-effective screening strategy for Down syndrome. If the cost of nuchal translucency is less than dollars 57 or when genetic sonogram is included in the second-trimester strategies, first-trimester combined screening became the most cost-effective strategy. LEVEL OF EVIDENCE: III.     

Tentative Identification of Bioactive Compounds From Aqueous Extract of Punica granatum Peel by HPLC/LC–MS Method

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The objective of this study was to carry out the phytochemical screening, antibacterial activity in different...     

Regenerative therapy for hippocampal degenerative diseases: lessons from preclinical studies

Increase in life expectancy has put neurodegenerative diseases on the rise. Amongst these, degenerative diseases involving hippocampus like Alzheimer's disease (AD) and temporal lobe epilepsy (TLE) are ranked higher as it is vulnerable to excitotoxicity induced neuronal dysfunction and death resulting in cognitive impairment. Modern medicines have not succeeded in halting the progression of these diseases rendering them incurable and often fatal. Under such scenario, regenerative studies employing stem cells or their by‐products in animal models of AD and TLE have yielded encourageing results. This review focuses on the distinct cell types, such as hippocampal cell lines, neural precursor cells, embryonic stem cells derived neural precursor cells, induced pluripotent stem cells, induced neurons and mesenchymal stem cells, which can be employed to rescue hippocampal functions in neurodegenerative diseases like AD and TLE. Besides, the divergent mechanisms through which cell based therapy confer neuroprotection, current impediments and possible improvements in stem cell transplantation strategies are discussed. Authors are aware of the voluminous literature available on this issue and have made a sincere attempt to put forth the current status of research in the field of cell based therapy concurrently discussing the promise it holds for combating neurodegenerative diseases like AD and TLE in the near future. Copyright © 2015 John Wiley & Sons, Ltd.     

Creatine CEST MRI for Differentiating Gliomas with Different Degrees of Aggressiveness

Purpose

Creatine (Cr) is a major metabolite in the bioenergetic system. Measurement of Cr using conventional MR spectroscopy (MRS) suffers from low spatial resolution and relatively long acquisition times. Creatine chemical exchange saturation transfer (CrCEST) magnetic resonance imaging (MRI) is an emerging molecular imaging method for tissue Cr measurements. Our previous study showed that the CrCEST contrast, obtained through multicomponent Z-spectral fitting, was lower in tumors compared to normal brain, which further reduced with tumor progression. The current study was aimed to investigate if CrCEST MRI can also be useful for differentiating gliomas with different degrees of aggressiveness.

Procedures

Intracranial 9L gliosarcoma and F98 glioma bearing rats with matched tumor size were scanned with a 9.4 T MRI scanner at two time points. CEST Z-spectra were collected using a customized sequence with a frequency-selective rectangular saturation pulse (B₁?=?50 Hz, duration?=?3 s) followed by a single-shot readout. Z spectral data were fitted pixel-wise with five Lorentzian functions, and maps of CrCEST peak amplitude, linewidth, and integral were produced. For comparison, single-voxel proton MR spectroscopy (¹H-MRS) was performed to quantify and compare the total Cr concentration in the tumor.

Results

CrCEST contrasts decreased with tumor progression from weeks 3 to 4 in both 9L and F98 phenotypes. More importantly, F98 tumors had significantly lower CrCEST integral compared to 9L tumors. On the other hand, integrals of other Z-spectral components were unable to differentiate both tumor progression and phenotype with limited sample size.

Conclusions

Given that F98 is a more aggressive tumor than 9L, this study suggests that CrCEST MRI may help differentiate gliomas with different aggressiveness.

     

Co‐precipitation of DEAE‐dextran coated SPIONs: how synthesis conditions affect particle properties,stem cell labelling and MR contrast

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as contrast agents for stem cell tracking using magnetic resonance imaging (MRI). The total mass of iron oxide that can be internalised into cells without altering their viability or phenotype is an important criterion for the generation of contrast, with SPIONs designed for efficient labelling of stem cells allowing for an increased sensitivity of detection. Although changes in the ratio of polymer and iron salts in co‐precipitation reactions are known to affect the physicochemical properties of SPIONs, particularly core size, the effects of these synthesis conditions on stem cell labelling and magnetic resonance (MR) contrast have not been established. Here, we synthesised a series of cationic SPIONs with very similar hydrodynamic diameters and surface charges, but different polymer content. We have investigated how the amount of polymer in the co‐precipitation reaction affects core size and modulates not only the magnetic properties of the SPIONs but also their uptake into stem cells. SPIONs with the largest core size and lowest polymer content presented the highest magnetisation and relaxivity. These particles also had the greatest uptake efficiency without any deleterious effect on either the viability or function of the stem cells. However, for all particles internalised in cells, the T₂ and T₂^* relaxivity was independent of the SPION's core size. Our results indicate that the relative mass of iron taken up by cells is the major determinant of MR contrast generation and suggest that the extent of SPION uptake can be regulated by the amount of polymer used in co‐precipitation reactions. Copyright © 2016 John Wiley & Sons, Ltd.     

Macrolide and fluoroquinolone mediated cardiac arrhythmias: clinical considerations and comprehensive review

While there is evidence for cardiac arrhythmias associated with macrolide and fluoroquinolone antibiotics, there is still debate among health care providers as to whether this risk of arrhythmia is overstated. A joint panel of the US Food and Drug Administration suggested that macrolide and fluoroquinolone labels need much stronger warnings regarding the possible serious adverse cardiac effects associated with these antibiotics, especially since they are so widely prescribed. And while health care providers may differ on the pertinence of the cardiac risks associated with antibiotic use, they can undoubtedly minimize the cardiac effects that are associated with these antibiotics by paying attention to the cardiac risk factors and drug history associated with the patient. Relevant studies for our review were identified from a PubMed search using keywords and combined word searches involving macrolides, fluoroquinolones, and cardiac arrhythmias. We attempted to include as many recent (>2015) articles as possible. We included case reports, randomized, controlled trials, observational studies, case-control studies, systematic reviews, and retrospective studies. Underlying cardiac issues can predispose patients to harmful cardiac side effects that can be exacerbated in the presence of antibiotics. The health care provider should rule out any risk factor associated with antibiotic-induced cardiac arrhythmia in the event that a patient does need a macrolide or fluoroquinolone antibiotic. Rigorous patient evaluation and a detailed patient history, including short and long term medication use, is the likely key to reducing any risk of cardiac arrhythmias associated with macrolides and fluoroquinolones. Clinicians should be cautious when prescribing macrolide and fluoroquinolone medications to patients with risk factors that may lead to antibiotic-induced cardiac arrhythmias, including a slow heart rate and those that are taking medications to treat arrhythmias.     

Effect of arylhydroxylamine metabolites of sulfamethoxazole and dapsone on stress signal expression in human keratinocytes

The initiation of an immune response to small molecules is believed to require the release of stress/danger signals that activate resident dendritic cells, presumably secondary to the formation of reactive metabolites. We hypothesized that exposure to arylhydroxylamine metabolites of dapsone and sulfamethoxazole lead to the expression/release of numerous stress signals in the skin. To test this hypothesis, we examined the effect of these metabolites on the expression of selected heat shock proteins, uric acid, cytokines, adhesion molecules, and costimulatory molecules in normal human epidermal keratinocytes (NHEKs). NHEKs showed a time-dependent up-regulation of heat shock protein 70 and translocation of heat shock protein 27 when exposed to the arylhydroxylamine metabolites. In addition, the secretion of several proinflammatory cytokines was increased upon incubation of these cells with metabolite. In contrast, the uric acid concentration was not altered. Moreover, intercellular adhesion molecule-1, CD80, and CD86 expressions did not change when NHEKs were exposed to these reactive metabolites. Our data suggest that NHEKs selectively up-regulate certain danger signals when exposed to arylhydroxylamine metabolites. These signals may subsequently activate dendritic cells and initiate an immune response within skin.     

Paediatric acute respiratory distress syndrome (PARDS)

Acute respiratory distress syndrome (ARDS) is a syndrome with acute, diffuse, inflammatory lung injury associated with non-haemodynamic lung oedema. It is responsible for almost a quarter of the ventilated patients in intensive care. The causes of ARDS are variable. They include primary pulmonary diseases such as pneumonia, drowning and aspiration and extra-pulmonary conditions including sepsis, trauma or burns. Although ARDS is well recognized in children, it is, in our experience, underdiagnosed in the paediatric intensive care units. This short article describes the diagnostic criteria, the causes and the management of ARDS in children.