Summary
Background
Advanced practice providers (APP) may be able to play a role in improving the linkage to care in patients with chronic hepatitis B (CHB), but data are limited.
Aim
To compare ...management of patients with CHB under APP‐assisted versus physician‐only care
Methods
This retrospective analysis identified patients with CHB infection from Optum's de‐identified Clinformatics® Data Mart Database (2003–2021) using ICD‐9/ICD‐10 codes. We compared the proportion of patients with CHB who had adequate evaluation for treatment (defined as ALT, HBV DNA, ± HBeAg), and the proportion of treatment‐eligible patients with CHB who received treatment between APP versus physician‐only care.
Results
We included 42,140 eligible patients (mean age: 51.9 ± 15.1; 56.1% male). Overall, 34.3% received APP care with increasing utilisation over time. Compared to physician‐only care, patients who also received APP care were more likely to have viral co‐infection, and more likely to have been seen by a specialist (72.1%). Overall, 62.8% and 56.2% of treatment‐eligible patients based on AASLD and EASL guidelines, respectively, received treatment. APP care patients were more likely to be treated (AASLD adjusted HR: 1.18, 95%CI: 1.03–1.34; EASL adjusted HR:1.24, 95%CI: 1.09–1.41) after adjustment for age, sex, race/ethnicity, viral dual infection, baseline cirrhosis/liver cancer, number of HBV DNA and alanine aminotransferase measurements, and physician provider type.
Conclusion
Treatment‐eligible patients with CHB receiving APP care were more likely to receive antiviral therapy. APP care may help to expand the pool of providers for patients with CHB, and to improve current suboptimal treatment rates.
Quality of care of chronic hepatitis B patients with private insurance in the US.
The current guidelines for malaria prevention and control during pregnancy in Africa is predicated on the prevention of infection and/or disease through intermittent preventive treatment in pregnancy ...(IPTp), insecticide-treated nets (ITNs) and effective malaria case diagnosis and management. Concerns that increasing SP resistance in some areas of SSA may have compromised IPTp-SP efficacy prompted this contemporaneous study, designed to assess the prevalence and risk factors of sub-microscopic infection in parturient women during the low transmission season in Mutengene, a rapidly growing semi-urban area in Southwest Region, Cameroon. Pregnant women originally reporting for the establishment of antenatal clinic care during the dry season were followed-up to term and their pregnancy outcomes recorded. About 2 ml of venous blood was collected for malaria diagnosis using PfHRP2/pLDH malaria rapid diagnostic kit and light microscopy. DNA was extracted from dried blood spots by the Chelex-100 method and the Plasmodium falciparum status detected by nested PCR amplification of the 18SrRNA gene using specific predesigned primers. Of the 300 women enrolled, the proportion of malaria parasite infected as determined by microscopy, RDT and PCR was 12.9%, 16.4% and 29.4% respectively, with 39.9% overall infected with P. falciparum by microscopy and/or RDT and/or PCR and a very low-density infection, averaging 271 parasites per microliter of blood. About 25.0% (68/272) of women who were negative by microscopy were positive by PCR (submicroscopic P. falciparum infection), with primigravidae and IPTp-SP non usage identified as independent risk factors for submicroscopic P. falciparum parasitaemia while fever history (aOR = 4.83, 95% CI = 1.28-18.22, p = 0.020) was associated with risk of malaria parasite infection overall. IPTp-SP use (p = 0.007) and dosage (p = 0.005) significantly influenced whether or not the participant will be malaria parasite negative or carry submicroscopic or microscopic infection. Although Infant birthweight and APGAR score were independent of the mother's P. falciparum infection and submicroscopic status, infant's birthweight varied with the gravidity status (p = 0.001) of the mother, with significantly lower birthweight neonates born to primigravidae compared to secundigravidae (p = 0.001) and multigravidae (p = 0.003). Even in holo-endemic dry season, there exists a large proportion of pregnant women with very low density parasitaemia. IPTp-SP seems to be relevant in controlling submicroscopic P. falciparum infections, which remains common in pregnant women, and are hard to diagnose, with potentially deleterious consequences for maternal and fetal health. Future studies should be carried out in hyperendemic malaria foci where the parasitemia levels are substantially higher in order to confirm the efficacy of IPTp-SP.
Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or ...L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na(+) conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined.
The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers.
G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p<0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p<0.005).
Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism.
Error detection in typing is crucial for assessing the adequacy of ongoing actions, leveraging both predictive mechanisms for early detection and sensory feedback for late detection. ...Neurophysiological studies have supported the anticipation of errors through predictive models. This research extends the understanding of error detection in typing, focusing on the neurocognitive mechanisms underlying errors in transparent and intransparent German words. Thirty-six volunteer students typed out aurally presented words, classified as either orthographically transparent or intransparent, on a computer keyboard without the possibility of correction. Because of poor spelling or excessive artifacts, the final sample comprised 27 participants. Event-related potentials (ERPs) were obtained time-locked to key presses, and behavioral data on typing correctness and speed were collected. A higher error rate and longer latency for intransparent words compared to transparent ones were found, suggesting the complexity of spelling impacts typing correctness. Post-error slowing was observed, aligning with increased cognitive control following errors. ERPs revealed a negative component akin to the error-related negativity (ERN) for typing errors, with a pronounced ERN-like negativity preceding erroneous key-presses, particularly for intransparent words. The study provides evidence of the cognitive and neural mechanisms underlying typing errors, highlighting the impact of orthographic transparency. The detection of an ERN-like negativity before erroneous key-presses, especially in typing intransparent words, underscores the brain's use of predictive mechanisms for error detection.
•Typing errors occur more frequently with intransparent than transparent words.•Post-error slowing indicates a rise in cognitive control.•ERN-like negativity shows predictive error detection in the brain.•Sensory feedback is not crucial for detecting typing errors.
The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the ...temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions were associated with an increase in proliferating neoplastic cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their neoplastic cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a myeloid cell state defined by specific ligand-receptor interactions with neoplastic cells. Collectively, these recurrence-associated phenotypes represent potential targets to alter disease progression.
Display omitted
•Longitudinal glioma evolution follows an IDH mutation-dependent trajectory•Hypermutation and CDKN2A deletions underlie increased proliferation at recurrence•Recurrent IDH-wild-type neoplastic cells up-regulate neuronal signaling programs•Mesenchymal transitions associate with distinct myeloid cell interactions
Integrating longitudinal transcriptomic and genomic data from paired diffuse glioma samples with complementary single-cell RNA-seq and multiplex immunofluorescence datasets reveals recurrence-associated genetic and microenvironmental changes that are dependent on IDH mutation status.
Plasmodium malariae, a neglected human malaria parasite, contributes up to 10% of malaria infections in sub-Saharan Africa (sSA). Though P. malariae infection is considered clinically benign, it ...presents mostly as coinfections with the dominant P. falciparum. Completion of its reference genome has paved the way to further understand its biology and interactions with the human host, including responses to antimalarial interventions. We characterized 75 P. malariae isolates from seven endemic countries in sSA using highly divergent microsatellites. The P. malariae infections were highly diverse and five subpopulations from three ancestries (independent of origin of isolates) were determined. Sequences of 11 orthologous antimalarial resistance genes, identified low frequency single nucleotide polymorphisms (SNPs), strong linkage disequilibrium between loci that may be due to antimalarial drug selection. At least three sub-populations were detectable from a subset of denoised SNP data from mostly the mitochondrial cytochrome b coding region. This evidence of diversity and selection calls for including P. malariae in malaria genomic surveillance towards improved tools and strategies for malaria elimination.
The current guidelines for malaria prevention and control during pregnancy in Africa is predicated on the prevention of infection and/or disease through intermittent preventive treatment in pregnancy ...(IPTp), insecticide-treated nets (ITNs) and effective malaria case diagnosis and management. Concerns that increasing SP resistance in some areas of SSA may have compromised IPTp-SP efficacy prompted this contemporaneous study, designed to assess the prevalence and risk factors of sub-microscopic infection in parturient women during the low transmission season in Mutengene, a rapidly growing semi-urban area in Southwest Region, Cameroon. Pregnant women originally reporting for the establishment of antenatal clinic care during the dry season were followed-up to term and their pregnancy outcomes recorded. About 2 ml of venous blood was collected for malaria diagnosis using PfHRP2/pLDH malaria rapid diagnostic kit and light microscopy. DNA was extracted from dried blood spots by the Chelex-100 method and the Plasmodium falciparum status detected by nested PCR amplification of the 18SrRNA gene using specific predesigned primers. Of the 300 women enrolled, the proportion of malaria parasite infected as determined by microscopy, RDT and PCR was 12.9%, 16.4% and 29.4% respectively, with 39.9% overall infected with P. falciparum by microscopy and/or RDT and/or PCR and a very low-density infection, averaging 271 parasites per microliter of blood. About 25.0% (68/272) of women who were negative by microscopy were positive by PCR (submicroscopic P. falciparum infection), with primigravidae and IPTp-SP non usage identified as independent risk factors for submicroscopic P. falciparum parasitaemia while fever history (aOR = 4.83, 95% CI = 1.28-18.22, p = 0.020) was associated with risk of malaria parasite infection overall. IPTp-SP use (p = 0.007) and dosage (p = 0.005) significantly influenced whether or not the participant will be malaria parasite negative or carry submicroscopic or microscopic infection. Although Infant birthweight and APGAR score were independent of the mother's P. falciparum infection and submicroscopic status, infant's birthweight varied with the gravidity status (p = 0.001) of the mother, with significantly lower birthweight neonates born to primigravidae compared to secundigravidae (p = 0.001) and multigravidae (p = 0.003). Even in holo-endemic dry season, there exists a large proportion of pregnant women with very low density parasitaemia. IPTp-SP seems to be relevant in controlling submicroscopic P. falciparum infections, which remains common in pregnant women, and are hard to diagnose, with potentially deleterious consequences for maternal and fetal health. Future studies should be carried out in hyperendemic malaria foci where the parasitemia levels are substantially higher in order to confirm the efficacy of IPTp-SP.
Hydrothermal synthesis is the state-of-the-art technique for the preparation of zeolites and related porous solids. However, when it comes to the preparation of nanosized zeolites, this technique is ...limited by low yields, separation problems and high amounts of waste. In this work, we utilized the strengths of a combination of spray drying and steam-assisted crystallization (SAC), also known as dry gel conversion, to reduce these problems. At spray drying temperatures between 300 and 400 °C, it was possible to convert all the amorphous material via SAC into zeolite particles without extra addition of template. Kinetic studies of SAC revealed that about 4 to 8 days are needed to achieve the formation of a 100% crystalline product. The newly formed crystalline phase was crystallized on the surface of the nanosized zeolites and led to a slight increase in the primary particle size while the macroscopic morphology of the spray-dried aggregates was preserved. This work demonstrates that the combination of spray drying and SAC are useful tools in supplementing the hydrothermal synthesis of nanosized zeolites.
Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs ...critical to elimination efforts. Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon.
Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional surveys from May 2013 to March 2014 along the slope of mount Cameroon. Plasmodium falciparum malaria parasitaemic blood, screened by light microscopy, was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq platform.
A total of 259 participants were enrolled in this study from three different altitudes. While some alleles associated with drug resistance in pfdhfr, pfmdr1 and pfcrt were highly prevalent, less than 3% of all samples carried mutations in the pfkelch13 gene, none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast Asia. The most prevalent haplotypes were triple mutants Pfdhfr I
R
N
I
(99%), pfcrt- C
V
I
E
T
(47.3%), and single mutants PfdhpsS
G
K
A
A
(69%) and Pfmdr1 N
F
D
(53.2%).
The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon.
PDF
