Παρασκευή 30 Οκτωβρίου 2020

Treatment of Epilepsy Associated with Periventricular Nodular Heterotopia

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Abstract

Purpose of Review

Epilepsy associated with periventricular nodular heterotopia (PNH), a developmental malformation, is frequently drug-resistant and requires focal therapeutic intervention. Invasive EEG study is usually necessary to delineate the epileptogenic zone, but constructing an accurate hypothesis to define an appropriate electrode implantation scheme and the treatment is challenging. This article reviews recent studies that help understanding the epileptogenicity and potential therapeutic options in PNH.

Recent Findings

New noninvasive diagnostic and intracerebral EEG analytic tools demonstrated that cortical hyperexcitability and aberrant connectivity (between nodules and cortices and among nodules) are likely mechanisms causing epilepsy in most patients. The deeply seated PNH, if epileptogenic, are ideal target for stereotactic ablative techniques, which offer concomitant ablation of multiple regions with relatively satisfactory seizure outcome.

Summary

Advance in diagnostic and analytic tools have enhanced our understanding of the complex epileptogenicity in PNH. Development in stereotactic ablative techniques now offers promising therapeutic options for these patients.

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Photosensitizer delivery by fibrin glue: potential for bypassing the blood-brain barrier

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Abstract

Fibrin glue (FG) has potential as a delivery vehicle for photosensitizer directly to the resection cavity, so it may bypass the blood-brain barrier (BBB) and increase the concentration of successfully delivered photosensitizer. A specialized form of photodynamic therapy (PDT), photochemical internalization (PCI), which involves both photosensitizer and chemotherapeutic agent internalization, can locally inhibit the growth of cells. This will allow the reduction of recurrence of malignant gliomas around surgical resection. This study will look at the efficacy of FG loaded with drugs in mediating both PDT and PCI in inhibiting 3-dimensional tumor spheroid growth in vitro. Experiments were conducted on spheroids comprised of F98 glioma cells using photosensitizer AlPcS2a and chemotherapeutic drug bleomycin (BLM). At 2-, 24-, 48-, and 72-h increments, supernatant covering an FG layer within a well was collected and replaced by fresh medium, then added to s pheroid-containing wells, which contained the respective chemicals for PDT and PCI. The wells were then exposed to light treatment from a diode laser, and after, spheroid growth was monitored for a period of 14 days. Significant spheroid growth inhibition was observed in both PDT and PCI modalities, but was far greater in PCI. Additionally, complete growth suppression was achieved via PCI at the highest radiant exposure. Achieving a slow photosensitizer release, significant F98 spheroid inhibition was observed in FG-mediated PDT and PCI. The present study showed BLM-PCI was the most efficacious of the two modalities.

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Using rapid point-of-care tests to inform antibiotic choice to mitigate drug resistance in gonorrhoea

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Background

The first cases of extensively drug resistant gonorrhoea were recorded in the United Kingdom in 2018. There is a public health need for strategies on how to deploy existing and novel antibiotics to minimise the risk of resistance development. As rapid point-of-care tests (POCTs) to predict susceptibility are coming to clinical use, coupling the introduction of an antibiotic with diagnostics that can slow resistance emergence may offer a novel paradigm for maximising antibiotic benefits. Gepotidacin is a novel antibiotic with known resistance and resistance-predisposing mutations. In particular, a mutation that confers resistance to ciprofloxacin acts as the 'stepping-stone' mutation to gepotidacin resistance.

Aim

To investigate how POCTs detecting Neisseria gonorrhoeae resistance mutations for ciprofloxacin and gepotidacin can be used to minimise the risk of resistance development to gepotidacin.

Methods

We use individual-based stochastic simulations to formally investigate the aim.

Results

The level of testing needed to reduce the risk of resistance development depends on the mutation rate under treatment and the prevalence of stepping-stone mutations. A POCT is most effective if the mutation rate under antibiotic treatment is no more than two orders of magnitude above the mutation rate without treatment and the prevalence of stepping-stone mutations is 1–13%.

Conclusion

Mutation frequencies and rates should be considered when estimating the POCT usage required to reduce the risk of resistance development in a given population. Molecular POCTs for resistance mutations and stepping-stone mutations to resistance are likely to become important tools in antibiotic stewardship.

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The contribution of HIV point-of-care tests in early HIV diagnosis: community-based HIV testing monitoring in Catalonia, 1995 to 2018

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Background

Community-based HIV testing services combined with the use of point-of-care tests (POCT) have the potential to improve early diagnosis through increasing availability, accessibility and uptake of HIV testing.

Aim

To describe community-based HIV testing activity in Catalonia, Spain, from 1995 to 2018, and to evaluate the impact of HIV POCT on the HIV continuum of care.

Methods

A community-based network of voluntary counselling and testing services in Catalonia, Spain has been collecting systematic data on activity, process and results since 1995. A descriptive analysis was performed on pooled data, describing the data in terms of people tested and reactive screening test results.

Results

Between 1995 and 2018, 125,876 HIV tests were performed (2.1% reactive). Since the introduction of HIV POCT in 2007, a large increase in the number of tests performed was observed, reaching 14,537 tests alone in 2018 (1.3% reactive). Men who have sex with men (MSM), as a proportion of all people tested, has increased greatly over time reaching 74.7% in 2018. The highest percentage of reactive tests was found in people who inject drugs followed by MSM. The contribution of community-based HIV testing to the overall total notified cases in the Catalonia HIV registry has gradually increased, reaching 37.9% in 2018, and 70% of all MSM cases. In 2018, the percentage of individuals with a reactive screening test who were linked to care was 89.0%.

Conclusion

Our study reinforces the important role that community-based HIV POCT has on the diagnosis of HIV in key populations.

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Positive rotavirus samples

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Background

Rapid diagnostic tests are commonly used by hospital laboratories in England to detect rotavirus (RV), and results are used to inform clinical management and support national surveillance of the infant rotavirus immunisation programme since 2013. In 2017, the Public Health England (PHE) national reference laboratory for enteric viruses observed that the presence of RV could not be confirmed by PCR in a proportion of RV-positive samples referred for confirmatory detection.

Aim

We aimed to compare the positivity rate of detection methods used by hospital laboratories with the PHE confirmatory test rate.

Methods

Rotavirus specimens testing positive at local hospital laboratories were re-tested at the PHE national reference laboratory using a PCR test. Confirmatory results were compared to original results from the PHE laboratory information management system.

Results

Hospital laboratories screened 70.1% (2,608/3,721) of RV samples using immunochromatographic assay (IC) or rapid tests, 15.5% (578/3,721) using enzyme immunoassays (EIA) and 14.4% (535/3,721) using PCR. Overall, 1,011/3,721 (27.2%) locally RV-positive samples referred to PHE in 2016 and 2017 failed RV detection using the PHE reference laboratory PCR test. Confirmation rates were 66.9% (1,746/2,608) for the IC tests, 87.4% (505/578) for the EIA and 86.4% (465/535) for the PCR assays. Seasonal confirmation rate discrepancies were also evident for IC tests.

Conclusions

This report highlights high false positive rates with the most commonly used RV screening tests and emphasises the importance of implementing verified confirmatory tests for RV detections. This has implications for clinical diagnosis and national surveillance.

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Antimicrobial resistance point-of-care testing for gonorrhoea treatment regimens: cost-effectiveness and impact on ceftriaxone use of five hypothetical strategies compared with standard care in England sexual health clinics

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Background

Widespread ceftriaxone antimicrobial resistance (AMR) threatens Neisseria gonorrhoeae (NG) treatment, with few alternatives available. AMR point-of-care tests (AMR POCT) may enable alternative treatments, including abandoned regimens, sparing ceftriaxone use. We assessed cost-effectiveness of five hypothetical AMR POCT strategies: A-C included a second antibiotic alongside ceftriaxone; and D and E consisted of a single antibiotic alternative, compared with standard care (SC: ceftriaxone and azithromycin).

Aim

Assess costs and effectiveness of AMR POCT strategies that optimise NG treatment and reduce ceftriaxone use.

Methods

The five AMR POCT treatment strategies were compared using a decision tree model simulating 38,870 NG-diagnosed England sexual health clinic (SHC) attendees; A micro-costing approach, representing cost to the SHC (for 2015/16), was employed. Primary outcomes were: total costs; percentage of patients given optimal treatment (regimens curing NG, without AMR); percentage of patients given non-ceftriaxone optimal treatment; cost-effectiveness (cost per optimal treatment gained).

Results

All strategies cost more than SC. Strategy B (azithromycin and ciprofloxacin (azithromycin preferred); dual therapy) avoided most suboptimal treatments (n = 48) but cost most to implement (GBP 4,093,844 (EUR 5,474,656)). Strategy D (azithromycin AMR POCT; monotherapy) was most cost-effective for both cost per optimal treatments gained (GBP 414.67 (EUR 554.53)) and per ceftriaxone-sparing treatment (GBP 11.29 (EUR 15.09)) but with treatment failures (n = 34) and suboptimal treatments (n = 706).

Conclusions

AMR POCT may enable improved antibiotic stewardship, but require net health system investment. A small reduction in test cost would enable monotherapy AMR POCT strategies to be cost-saving.

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Τετάρτη 28 Οκτωβρίου 2020

A complicated pulmonary hydatid cyst resembling a tumour in an adult on PET scan: a case report

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Abstract
Complicated pulmonary cysts have a wide range of possible diagnoses with different approaches as they can be benign or malignant. They can resemble malignancies in symptoms and imaging, mainly on positron emission tomography (PET) scan, which can increase the false positivity. We present an infected hydatid cyst resembling a malignancy as it presented with weight loss in a smoker and had necrosis and malignance features on computed tomography and PET scans. However, serology tests and fine needle aspiration were suggestive of a hydatid cyst, which made this case quite unique. Other diagnoses should always be suspected even if the malignancy was highly likely due to other lesions can resemble malignancies.
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