Performance evaluation of Bruker UMIC® microdilution panel and disc diffusion to determine cefiderocol susceptibility in Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter xylosoxidans and Burkolderia species.

PURPOSE: Cefiderocol susceptibility testing (AST) represents an open challenge for clinical microbiology. Herein, we evaluated the performance of the UMIC® Cefiderocol broth microdilution (BMD) test and disc diffusion on Gram-negative species. METHODS: UMIC® Cefiderocol BMD test, disc diffusion and reference BMD were in parallel performed on a collection of 256 clinical isolates. Categorical agreement (CA), essential agreement (EA), bias, major errors (MEs) and very major errors (VMEs) were calculated for both AST methods. RESULTS: The UMIC® Cefiderocol BMD strip exhibited an EA < 90% (85.5%), a CA higher than 90% (93.7%) and a low number of VMEs (n = 4, 4.2%) and MEs (n = 12, 7.4%). UMIC® Cefiderocol identified 96.2% of the resistant isolates [Enterobacterales, (39/40); P. aeruginosa (19/19); A. xylosoxidans (5/6); S. maltophilia (5/6); Burkholderia spp. (8/8)]. Disc diffusion showed a high CA (from 94.9 to 100%) regardless of disc manufacturer in Enterobacterales, P. aeuroginosa, A. baumannii and S. maltophilia. However, high rates of results falling in the area of technical uncertainty (ATU) were observed in Enterobacterales (34/90, 37.8%) and P. aeruginosa (16/40, 40%). Disc diffusion showed a poor performance in A. xylosoxidans and Burkholderia spp. if PK/PD breakpoint was used (overall, 5/9 VMEs; in contrast, the use of P. aeruginosa-specific breakpoints resulted in 100% of CA with 24.6% of results in the ATU). CONCLUSION: In conclusion, disc diffusion and UMIC® Cefiderocol are valid methods for the determination of cefiderocol susceptibility. Given the high number of results in the ATU by disc diffusion, a combined use of both AST methods may represent a solution to overcome the challenge of cefiderocol susceptibility testing in routine microbiology laboratories.

Colorectal Cancer (CRC) treatment and associated costs in the public sector compared to the private sector in Johannesburg, South Africa.

BACKGROUND: South Africa's divided healthcare system is believed to be inequitable as the population serviced by each sector and the treatment received differs while annual healthcare expenditure is similar. The appropriateness of treatment received and in particular the cost of the same treatment between the sectors remains debatable and raises concerns around equitable healthcare. Colorectal cancer places considerable pressure on the funders, yet treatment utilization data and the associated costs of non-communicable diseases, in particular colorectal cancer, are limited for South Africa. Resources need to be appropriately managed while ensuring equitable healthcare is provided regardless of where the patient is able to receive their treatment. Therefore the aim of this study was to determine the cost of colorectal cancer treatment in a privately insured patient population in order to compare the costs and utilization to a previously published public sector patient cohort. METHODS: Private sector costs were determined using de-identified claim-based data for all newly diagnosed CRC patients between 2012 and 2014. The costs obtained from this patient cohort were compared to previously published public sector data for the same period. The costs compared were costs incurred by the relevant sector funder and didn't include out-of-pocket costs. RESULTS: The comparison shows private sector patients gain access to more of the approved regimens (12 vs. 4) but the same regimens are more costly, for example CAPOX costs approximately €150 more per cycle. The cost difference between 5FU and capecitabine monotherapy is less than €30 per cycle however, irinotecan is cheaper in comparison to oxaliplatin in the private sector (FOLFOX approx. €500 vs. FOLFIRI aprox. €460). Administrative costs account for up to 45% of total costs compared to the previously published data of these costs totaling < 15% of the full treatment cost in South Africa's public healthcare system. CONCLUSION: This comparison highlights the disparities between sectors while illustrating the need for further research to improve resource management to attain equitable healthcare.

Comparative evaluation of the UMIC Colistine kit to assess MIC of colistin of gram-negative rods.

BACKGROUND: The recent description of the first plasmid-mediated colistin-resistant gene mcr-1, conferring transferable and low-level resistance to colistin, raised concern about the need to implement a rapid and reliable screening method to detect colistin-resistant clinical isolates. The only valid method to assess the MIC of colistin is the broth microdilution according to the joint CLSI-EUCAST Polymyxin Breakpoints Working Group. UMIC Colistine is a ready-to-use broth microdilution kit developed to easily assess colistin MIC by proposing unitary polystyrene strips containing 11 concentrations of dehydrated colistin. Here, we evaluated the UMIC Colistine kit on 235 Gram-negative rods (176 Enterobacterales, including 70 harboring a mcr gene, and 59 non-fermentative), through comparison to the reference broth microdilution method prepared in accordance with EN ISO 20776-1:2006 standard. Reproducibility of the UMIC Colistine was assayed with the three recommended quality control strains E. coli ATCC 25922, E. coli NCTC 13846 (mcr-1 positive), and P. aeruginosa ATCC 27853, as for stability testing. RESULTS: Categorical agreement was 100% with 63.4% (n = 149) of colistin-resistant strains, and 36.6% (n = 86) of colistin-susceptible strains with both methods (S ≤ 2 µg/mL and R > 2 µg/mL). No major error or very major error was reported. Essential agreement was 94.0% (n = 221), and 100% for detection of colistin-resistant strains as compared to the reference method. Pearson's correlation between UMIC Colistine and the reference method was 0.98. Reproducibility of the UMIC Colistine system was 97.8% with MICs of the quality control strains within the target ranges. However, some isolates had lower MIC with UMIC Colistine, but that did not change their categorization as colistin-susceptible, and this phenomenon should be further explored. CONCLUSIONS: The UMIC Colistine kit is an easy to perform unitary device that showed excellent results when compared to the reference method. The UMIC Colistine system is a rapid and reliable broth microdilution method that is suitable to assess the colistin MIC of clinical isolates in clinical microbiology laboratories.

Identifying barriers to treatment of childhood rhabdomyosarcoma in resource-limited settings: A literature review.

We performed a literature review to examine barriers for rhabdomyosarcoma treatment in low-resource settings, and identified 29 articles from 14 middle-income countries, with none from low-income countries. Notable findings included inconsistent use of local control modalities, lack of diagnostics in some settings, and high rate of abandonment specifically in low middle-income countries. Reported limitations included lack of surgical expertise and/or radiation therapy, advanced stage of disease, and absence of health insurance. Although very poor outcomes were prevalent in several settings, good outcomes were achievable in others when multidisciplinary therapy and financial coverage of medical care were made available.

Pediatric neurosurgical workforce, access to care, equipment and training needs worldwide.

OBJECTIVE: The presence and capability of existing pediatric neurosurgical care worldwide is unknown. The objective of this study was to solicit the expertise of specialists to quantify the geographic representation of pediatric neurosurgeons, access to specialist care, and equipment and training needs globally. METHODS: A mixed-question survey was sent to surgeon members of several international neurosurgical and general pediatric surgical societies via a web-based platform. Respondents answered questions on 5 categories: surgeon demographics and training, hospital and practice details, surgical workforce and access to neurosurgical care, training and equipment needs, and desire for international collaboration. Responses were anonymized and analyzed using Stata software. RESULTS: A total of 459 surgeons from 76 countries responded. Pediatric neurosurgeons in high-income and upper-middle-income countries underwent formal pediatric training at a greater rate than surgeons in low- and lower-middle-income countries (89.5% vs 54.4%). There are an estimated 2297 pediatric neurosurgeons in practice globally, with 85.6% operating in high-income and upper-middle-income countries. In low- and lower-middle-income countries, roughly 330 pediatric neurosurgeons care for a total child population of 1.2 billion. In low-income countries in Africa, the density of pediatric neurosurgeons is roughly 1 per 30 million children. A higher proportion of patients in low- and lower-middle-income countries must travel > 2 hours to seek emergency neurosurgical care, relative to high-income countries (75.6% vs 33.6%, p < 0.001). Vast basic and essential training and equipment needs exist, particularly low- and lower-middle-income countries within Africa, South America, the Eastern Mediterranean, and South-East Asia. Eighty-nine percent of respondents demonstrated an interest in international collaboration for the purposes of pediatric neurosurgical capacity building. CONCLUSIONS: Wide disparity in the access to pediatric neurosurgical care exists globally. In low- and lower-middle-income countries, wherein there exists the greatest burden of pediatric neurosurgical disease, there is a grossly insufficient presence of capable providers and equipped facilities. Neurosurgeons across income groups and geographic regions share a desire for collaboration and partnership.

Arsenic Removal Using Unconventional Material with Iron Content: Batch Adsorption and Column Study.

The remediation of arsenic contamination in potable water is an important and urgent concern, necessitating immediate attention. With this objective in mind, the present study investigated arsenic removal from water using batch adsorption and fixed-bed column techniques. The material employed in this study was a waste product derived from the treatment of groundwater water for potable purposes, having a substantial iron composition. The material's properties were characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Fourier-transformed infrared spectroscopy (FT-IR). The point of zero charge (pHPZC) was measured, and the pore size and specific surface area were determined using the BET method. Under static conditions, kinetic, thermodynamic, and equilibrium studies were carried out to explore the influencing factors on the adsorption process, namely the pH, contact time, temperature, and initial arsenic concentration in the solution. It was found that the adsorption process is spontaneous, endothermic, and of a physical nature. In the batch adsorption studies, the maximum removal percentage was 80.4% after 90 min, and in a dynamic regime in the fixed-bed column, the efficiency was 99.99% at a sludge:sand = 1:1 ratio for 380 min for a volume of water with arsenic of ~3000 mL. The kinetics of the adsorption process conformed to a pseudo-second-order model. In terms of the equilibrium studies, the Sips model yielded the most accurate representation of the data, revealing a maximum equilibrium capacity of 70.1 mg As(V)/g sludge. For the dynamic regime, the experimental data were fitted using the Bohart-Adams, Thomas, and Clark models, in order to establish the mechanism of the process. Additionally, desorption studies were conducted, serving as an essential step in validating the practical applicability of the adsorption process, specifically in relation to the reutilization of the adsorbent material.

Gene therapy for selected neuromuscular and trinucleotide repeat disorders - An insight to subsume South Asia for multicenter clinical trials.

Background: In this article, the authors discuss how they utilized the genetic mutation data in Sri Lankan Duchenne muscular dystrophy (DMD), Spinal muscular atrophy (SMA), Spinocerebellar ataxia (SCA) and Huntington's disease (HD) patients and compare the available literature from South Asian countries to identifying potential candidates for available gene therapy for DMD, SMA, SCA and HD patients. Methods: Rare disease patients (n = 623) with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy were genetically confirmed using Multiplex Ligation Dependent Probe Amplification (MLPA), and single plex PCR. A survey was conducted in the "Wiley database on Gene Therapy Trials Worldwide" to identify DMD, SMA, SCA, and HD gene therapy clinical trials performed worldwide up to April 2021. In order to identify candidates for gene therapy in other neighboring countries we compared our findings with available literature from India and Pakistan which has utilized the same molecular diagnostic protocol to our study. Results: From the overall cohort of 623 rare disease patients with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy, n = 343 (55%) [Muscular Dystrophy- 65%; (DMD-139, Becker Muscular Dystrophy -BMD-11), SCA type 1-3-53% (SCA1-61,SCA2- 23, SCA3- 39), HD- 52% (45) and SMA- 34% (22)] patients were positive for molecular diagnostics by MLPA and single plex PCR. A total of 147 patients in Sri Lanka amenable to available gene therapy; [DMD-83, SMA-15 and HD-49] were identified. A comparison of Sri Lankan finding with available literature from India and Pakistan identified a total of 1257 patients [DMD-1076, SMA- 57, and HD-124] from these three South Asian Countries as amenable for existing gene therapy trials. DMD, SMA, and HD gene therapy clinical trials (113 studies) performed worldwide up to April 2021 were concentrated mostly (99%) in High Income Countries (HIC) and Upper Middle-Income Countries (UMIC). However, studies on the potential use of anti-sense oligonucleotides (ASO) for treatment of SCAs have yet to reach clinical trials. Conclusion: Most genetic therapies for neurodegenerative and neuromuscular disorders have been evaluated for efficacy primarily in Western populations. No multicenter gene therapy clinical trial sites for DMD, SMA and HD in the South Asian region, leading to lack of knowledge on the safety and efficacy of such personalized therapies in other populations, including South Asians. By fostering collaboration between researchers, clinicians, patient advocacy groups, government and industry in gene therapy initiatives for the inherited-diseases community in the developing world would link the Global North and Global South and breathe life into the motto "Together we can make a difference".