Summary
Background
The temporal relationship between nucleoside analogue therapy for chronic hepatitis B (CHB) and liver cancer development has not been evaluated at a population level.
Aim
To ...investigate the impact of nucleoside analogue prescription on liver cancer incidence in a CHB‐prevalent region.
Methods
We obtained territory‐wide nucleoside analogue prescription data from 1999, when nucleoside analogue was first available in Hong Kong, to 2012 and the population‐based liver cancer incidence data from 1990 to 2012. We compared the liver cancer incidences from 1990 to 1998 and 1999 to 2012 with adjustment for local hepatitis B surface antigen seroprevalence.
Results
Nucleoside analogue prescription patient headcount increased from 2006 per year in 1999 to 26 411 in 2012. Prescription volume in 2012 was highest among 55–64 years (30.3%), higher than 65–74 years (13.0%) and ≥75 years (5.8%). Age‐standardised liver cancer incidence 1999–2012 decreased by 1.88%/year (95% CI 3.34% to 0.42%/year). NA therapy was associated with decline in age‐adjusted liver cancer incidence (2.7 per 100 000 persons, P < 0.001, 95% CI 1.4–4.0 per 100 000 persons). Fifty‐five to sixty‐four years age group had the most significant decline (men: 24.0 per 100 000 persons, P = 0.001, 95% CI 11.4–36.6 per 100 000 persons; women: 8.5 per 100 000 persons, P = 0.009, 95% CI 2.3–14.6 per 100 000 persons). No significant association was noted in age groups 65–74 years and ≥75 years (both P > 0.05).
Conclusions
Nucleoside analogue prescription was associated with a reduction of overall liver cancer incidence in a CHB‐prevalent region. The lack of association among individuals of ≥65 years was consistent with the low nucleoside analogue prescription volume in elderly patients, mitigating the impact of CHB treatment on liver cancer.
Linked ContentThis article is linked to Xuan et al paper. To view this article visit https://doi.org/10.1111/apt.14025.
Osteonecrosis of the femoral head is the most common diagnosis leading to total hip arthroplasty in young adults. Joint-preserving treatment options have been mainly surgical, with inconsistent ...results. Alendronate (a bisphosphonate agent) has been shown to lower the prevalence of vertebral compression fractures and could potentially retard the collapse of an osteonecrotic femoral head. The purpose of this study was to test the effect of alendronate in preventing early collapse of the femoral head in patients with nontraumatic osteonecrosis.
Forty patients with Steinberg stage-II or III nontraumatic osteonecrosis of the femoral head and a necrotic area of >30% (class C) were randomly divided into alendronate and control groups of twenty patients each. Patients in the alendronate group took 70 mg of alendronate orally per week for twenty-five weeks, while the patients in the control group did not receive this medication or a placebo. The patients were observed for a minimum of twenty-four months. Harris hip scores, plain radiographs, and magnetic resonance imaging scans were obtained.
During the study period, only two of twenty-nine femoral heads in the alendronate group collapsed, whereas nineteen of twenty-five femoral heads in the control group collapsed (p < 0.001). One hip in the alendronate group underwent total hip arthroplasty, whereas sixteen hips in the control group underwent total hip arthroplasty (p < 0.001).
Alendronate appeared to prevent early collapse of the femoral head in the hips with Steinberg stage-II or IIIC nontraumatic osteonecrosis. A longer duration of follow-up is needed to confirm whether alendronate prevents or only retards collapse.
Therapeutic Level I.
Abstract
We present panchromatic observations and modeling of calcium-strong supernovae (SNe) 2021gno in the star-forming host-galaxy NGC 4165 and 2021inl in the outskirts of elliptical galaxy NGC ...4923, both monitored through the Young Supernova Experiment transient survey. The light curves of both, SNe show two peaks, the former peak being derived from shock cooling emission (SCE) and/or shock interaction with circumstellar material (CSM). The primary peak in SN 2021gno is coincident with luminous, rapidly decaying X-ray emission (
L
x
= 5 × 10
41
erg s
−1
) detected by Swift-XRT at
δ
t
= 1 day after explosion, this observation being the second-ever detection of X-rays from a calcium-strong transient. We interpret the X-ray emission in the context of shock interaction with CSM that extends to
r
< 3 × 10
14
cm. Based on X-ray modeling, we calculate a CSM mass
M
CSM
= (0.3−1.6) × 10
−3
M
⊙
and density
n
= (1−4) × 10
10
cm
−3
. Radio nondetections indicate a low-density environment at larger radii (
r
> 10
16
cm) and mass-loss rate of
M
̇
<
10
−
4
M
⊙
yr
−1
. SCE modeling of both primary light-curve peaks indicates an extended-progenitor envelope mass
M
e
= 0.02−0.05
M
⊙
and radius
R
e
= 30−230
R
⊙
. The explosion properties suggest progenitor systems containing either a low-mass massive star or a white dwarf (WD), the former being unlikely given the lack of local star formation. Furthermore, the environments of both SNe are consistent with low-mass hybrid He/C/O WD + C/O WD mergers.
Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of ...movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis.
We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation.
A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.
Ground-based measurements of atmospheric trace gas species and criteria pollutants are essential for understanding emissions dynamics across space and time. Gas composition in the lower 50 m of the ...atmosphere has the greatest direct impacts on human health as well as ecosystem processes; hence data at this level are necessary for addressing carbon-cycle- and public-health-related questions. However, such surface data are generally associated with stationary measurement towers, where spatial representation is limited due to the high cost of establishing and maintaining an extensive network of measurement stations. We describe here a compact mobile laboratory equipped to provide high-precision, high-frequency, continuous, on-road synchronous measurements of CO2, CO, CH4, H2O, NOx, O3, aerosol, meteorological, and geospatial position data. The mobile laboratory has been deployed across the western USA. In addition to describing the vehicle and its capacity, we present data that illustrate the use of the laboratory as a powerful tool for investigating the spatial structure of urban trace gas emissions and criteria pollutants at spatial scales ranging from single streets to whole ecosystem and regional scales. We assess the magnitude of known point sources of CH4 and also identify fugitive urban CH4 emissions. We illustrate how such a mobile laboratory can be used to better understand emissions dynamics and quantify emissions ratios associated with trace gas emissions from wildfire incidents. Lastly, we discuss additional mobile laboratory applications in health and urban metabolism.
Amorphous InGaZnO (a-IGZO) UV photodetectors with a metal-semiconductor-metal structure were fabricated on polyethylene terephthalate (PET) substrates, and the effects of surface fluorine plasma ...treatment on a-IGZO were investigated. With this treatment, the oxygen vacancies (O vac 's) at the a-IGZO surface were effectively passivated, thus reducing the shallow-level donor states and electron traps. Accordingly, the direct and/or trap assisted tunnelings through the metal/a-IGZO Schottky barrier were suppressed, leading to a significant reduction in the dark current. On the other hand, the photo current was nearly unchanged if the treatment time was less than 20 min. It is due to the simultaneous reductions in hole trap and recombination center, both of which are related to the Ovac's at deep levels. As a result, a high detectivity of 4.36 × 10 13 Jones was realized with an increase of nearly 10 times. Moreover, a highly uniform trap distribution was achieved, and it could be beneficial to the photoconductive reliability of the device.
Curcumin (diferuloylmethane), a yellow substance from the root of the plant Curcuma longa Linn., has been demonstrated to inhibit carcinogenesis of murine skin, stomach, intestine and liver. However, ...the toxicology, pharmacokinetics and biologically effective dose of curcumin in humans have not been reported. This prospective phase-I study evaluated these issues of curcumin in patients with one of the following five high-risk conditions: 1) recently resected urinary bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5) intestinal metaplasia of the stomach. Curcumin was taken orally for 3 months. Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treament. The starting dose was 500 mg/day. If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of curcumin in serum and urine was determined by high pressure liquid chromatography (HPLC). A total of 25 patients were enrolled in this study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients. The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of crucumin and gradually declined within 12 hours. The average peak serum concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were 0.51 +/- 0.11 microM, 0.63 +/- 0.06 microM and 1.77 +/- 1.87 microM, respectively. Urinary excretion of curcumin was undetectable. One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment. In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out of 6 patients of intestinal metaplasia of the stomach, I out of 4 patients with CIN and 2 out of 6 patients with Bowen's disease. In conclusion, this study demonstrated that curcumin is not toxic to humans up to 8,000 mg/day when taken by mouth for 3 months. Our results also suggest a biologic effect of curcumin in the chemoprevention of cancer.
The limited sensitivity of serological tests for mycobacterial antigens has encouraged the development of a nanoparticle probe specific for the extrapulmonary form of Mycobacterium tuberculosis ...(Mtb). We developed an innovative probe comprised of super-paramagnetic iron oxide (SPIO) nanoparticles conjugated with Mtb surface antibody (MtbsAb-nanoparticles) to provide ultrasensitive imaging of biomarkers involved in extrapulmonary Mtb infection. MtbsAb-nanoparticles were significantly conjugated with Mtb bacilli. The extent of contrast enhancement reduction on magnetic resonance imaging (MRI) for Mtb and human monocytic THP1 cells was proportional to the concentration of MtbsAb-nanoparticles. When MtbsAb-nanoparticles were intravenously injected into mice bearing Mtb granulomas, the granulomatous site showed a 14-fold greater reduction in signal intensity enhancement on T2-weighted MR images compared with an opposing site that received PBS injection. Mtb sAb-nanoparticles represent a new non-invasive technology for the diagnosis of extrapulmonary Mtb.
BackgroundPrimary pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae is an emerging infectious disease. Capsular serotype K1 and the magA gene have been reported to be associated with this ...disease MethodsThe prevalence of magA was determined by polymerase chain reaction (PCR). The sequences of the magA flanking region were completed by inverse PCR and direct sequencing. Serotyping was performed by double immunodiffusion. Insertion mutations and trans-complementation were used to define the K1 genetic determination region ResultsThirty-five of 42 strains from patients with PLA were magA positive, whereas only 1 of 32 non-PLA strains was magA positive. All 36 magA-positive strains were serotype K1, and the 38 magA-negative strains were not (36/36 vs. 0/38; P<.0001). Sequencing of the magA flanking region revealed a putative capsular polysaccharide synthesis (cps) region; this region was 25 kb in length and contained 20 open reading frames (ORFs); of these ORFs, 9 were cotranscribed as part of an operon and differed from both MGH78578 and the Chedid strain. Mutation of 4 genes in this region turned the mutant strains anti-K1 negative. Trans-complementation restored the K1 phenotype ConclusionsThe operon containing magA is responsible for capsular serotype K1 of K. pneumoniae Several loci in the operon are unique determinants of K1 strains
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