Comparison of the efficacy of febuxostat vs. benzbromarone in the treatment of gout: a meta-analysis in Chinese gout patients.

OBJECTIVE: Febuxostat and benzbromarone are two common drugs for the treatment of gout, but the clinical efficacy of these two drugs is controversial. This meta-analysis aimed to compare the efficacy of febuxostat and benzbromarone in the treatment of gout. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for articles related to febuxostat and benzbromarone in the treatment of gout from inception to January 7, 2023. Titles and abstracts were reviewed in accordance with predesigned inclusion and exclusion criteria, and data were extracted independently. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies, and the continuous variables were expressed as the standard mean square error (SMD) by STATA 16 (Stata Corp., College Station, TX, USA). The sensitivity analysis was conducted by randomly removing a study, and the heterogeneity was analyzed by funnel plots and Egger's test. RESULTS: According to the search strategy, a total of 1,043 publications were retrieved from the three aforementioned databases, of which 45 publications were excluded due to duplication. Fourteen studies remained after screening titles and abstracts, and a total of 7 studies met the inclusion criteria after a comprehensive evaluation of the 14 studies. Meta-analysis showed that the uric acid (UA)-reducing effect of febuxostat is better than that of benzbromarone, while febuxostat showed a better ability to improve the estimated glomerular filtration rate (eGFR) and reduce Cr and blood urea nitrogen (BUN). In terms of hepatotoxicity, benzbromarone was not as potent as febuxostat in increasing alanine transaminase (ALT) and aspartate transaminase (AST), suggesting that benzbromarone has less hepatotoxicity. Moreover, there was no significant difference in the effect on blood lipid levels between the two drugs. CONCLUSIONS: The beneficial effect of febuxostat on renal function-related indexes such as the eGFR, Cr and BUN is significant, while benzbromarone is more effective in reducing UA and has relatively less hepatotoxicity. The specific efficacy of the two drugs needs to be confirmed by further research.

Reminder through mobile messaging application improves outpatient attendance and medication adherence among patients with depression: An open-label randomised controlled trial.

INTRODUCTION: Non-attendance and medication adherence are longstanding concerns in psychiatric outpatient settings. This study aimed to determine effectiveness of reminders using mobile messaging applications (messaging apps) in improving outpatient attendance and medication adherence among patients with depression. METHODS: This was a parallel, open-label randomised controlled trial with participants recruited from psychiatric outpatient services of a teaching hospital in Kuala Lumpur and a secondary hospital in Melaka. Adults (≥18 years) diagnosed with major depressive disorder; capable of reading and understanding English or Bahasa Malaysia; prescribed with at least one antidepressant and owns a smart phone were subsequently randomly assigned (1:1) to receive treatment reminders (intervention) or standard treatment without reminders (control), using a computergenerated randomisation programme. The intervention group received two reminder categories: Outpatient appointment reminders (a day before appointment); and medication reminders (weekly basis). Participants were followed-up over two months. We utilised Montgomery- Asberg Depression Rating Scale (MADRS) to measure the severity of depression; and Brief Adherence Rating Scale (BARS) to assess medication adherence. Primary outcomes were outpatient attendance rates and medication adherence assessed at two months. Secondary outcomes included changes in depression severity within each group at two months; comparison of changes in depression severity between both groups; preferences of participants towards treatment reminders, and reasons for non-attendance among participants. This trial was registered with the National Medical Research Registry, NMRR-19-3466-52001. RESULTS: Between February and April 2020, 183 participants were randomised to each group, of whom 179 reached study endpoint (91 [98.9%] of 92 in intervention group and 88 [96.7%] of 91 in control group). All recruited participants (n=183) were analysed using intention-to-treat approach. At two months, intervention group has significantly higher outpatient attendance rates (76.8%) than control group (56.4%) (p=0.002), and reported higher medical adherence percentage (mean difference 23.1, [95%CI 0.4, 35.8]; p<0.001). There was also significant difference in the MADRS score change between both groups (mean difference 3.4, [95%CI 0.4, 6.3]; p=0.025). Treatment reminders preferences among participants varied; forgetfulness was the most commonly reported reason (53%) for missing outpatient appointments. CONCLUSION: Reminders through mobile messaging applications significantly improved outpatient attendance and medication adherence among patients with depression. Our findings support the use of messaging apps for treatment reminders in psychiatric outpatient settings. However, concerns regarding confidentiality require careful measures to be taken.

MiR-124 regulates osteoblast differentiation through GSK-3ß in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a spastic and spinal joint disease with the characteristic of pathological ossification. Bioinformatics analysis demonstrated that there is a complementary binding site between microRNA-124 (miR-124) and the 3'-UTR of glycogen synthase kinase-3ß (GSK-3ß) mRNA. We aimed to investigate the role of miR-124 in regulating GSK-3ß expression, Wnt/ß-catenin pathway activity, and osteoblast differentiation of spinal ligament fibroblasts. PATIENTS AND METHODS: The ligament tissues of AS and the femoral neck fracture patients were collected. MiR-124 and GSK-3ß mRNA expressions were detected by using quantitative Real-time PCR (qRT-PCR). GSK-3ß and ß-catenin protein expressions were detected by using Western blot. Ligament fibroblasts were isolated and induced to differentiate into osteoblasts. Alizarin red S staining (ARS) was used to identify osteoblast differentiation. Expressions of miR-124, GSK-3ß, ß-catenin, Osterix, and runt-related transcription factor 2 (RUNX2) were detected during differentiation. The cells were divided into two groups as agomiR-normal control (NC) transfection group and agomir miR-124 transfection group. Alkaline phosphatase (ALP) activity and Alizarin Red S staining were detected. RESULTS: MiR-124 and ß-catenin expressions in the ligament of AS patients increased, while GSK-3ß level reduced compared with control. MiR-124, ß-catenin, Osterix, and RUNX2 expressions gradually elevated, whereas GSK-3ß level gradually declined following increased osteoblasts differentiation. Antagomir miR-124 transfection significantly up-regulated the expression of GSK-3ß in osteoblast differentiation, significantly decreased the expression of ß-catenin, Osterix, and RUNX2, and significantly inhibited osteoblast differentiation. CONCLUSIONS: MiR-124 decreased and GSK-3ß elevated in AS ligament tissue. Down-regulation of miR-124 expression enhanced GSK-3ß expression, weakened Wnt/ß-catenin pathway activity, and inhibited the differentiation of ligament fibroblasts into osteoblasts.

Prevention of ventilator-associated pneumonia.

Ventilator-associated pneumonia is the commonest, yet mostly preventable, infection in mechanically ventilated patients. Successful control of ventilator-associated pneumonia can save hospitalisation cost, and is possible by using a multidisciplinary clinical and administrative approach. The ventilator-associated pneumonia rate should be expressed as the number of ventilator-associated pneumonia days per 1000 ventilator days to take into account the device-utilisation duration for meaningful comparison. Various strategies address the issue, including general infection control measures, body positioning, intubation and mechanical ventilation, oral and gastro-intestinal tract, endotracheal tube, airway pressure, cuff pressure, selective digestive and/or oropharyngeal decontamination, and probiotic or early antibiotic treatment, as well as overall administration at a policy level. The rationale and controversy of these approaches are discussed in this article. The authors suggest that all units treating mechanically ventilated patients should have a ventilator-associated pneumonia prevention protocol in place, and ventilator-associated pneumonia should be seriously considered as a key performance indicator in local intensive care units.

ViQuaS: an improved reconstruction pipeline for viral quasispecies spectra generated by next-generation sequencing.

MOTIVATION: The combined effect of a high replication rate and the low fidelity of the viral polymerase in most RNA viruses and some DNA viruses results in the formation of a viral quasispecies. Uncovering information about quasispecies populations significantly benefits the study of disease progression, antiviral drug design, vaccine design and viral pathogenesis. We present a new analysis pipeline called ViQuaS for viral quasispecies spectrum reconstruction using short next-generation sequencing reads. ViQuaS is based on a novel reference-assisted de novo assembly algorithm for constructing local haplotypes. A significantly extended version of an existing global strain reconstruction algorithm is also used. RESULTS: Benchmarking results showed that ViQuaS outperformed three other previously published methods named ShoRAH, QuRe and PredictHaplo, with improvements of at least 3.1-53.9% in recall, 0-12.1% in precision and 0-38.2% in F-score in terms of strain sequence assembly and improvements of at least 0.006-0.143 in KL-divergence and 0.001-0.035 in root mean-squared error in terms of strain frequency estimation, over the next-best algorithm under various simulation settings. We also applied ViQuaS on a real read set derived from an in vitro human immunodeficiency virus (HIV)-1 population, two independent datasets of foot-and-mouth-disease virus derived from the same biological sample and a real HIV-1 dataset and demonstrated better results than other methods available.

Optical and magneto-optical anisotropies in large-area two-dimensional Co antidots film.

In this work, we investigate the plasmon-induced optical and magneto-optical anisotropies in the large-area square-ordered Co antidots film. It shows that both the outline of reflectivity spectrum and Kerr spectrum are significantly modified by surface plasmon polarition (SPP) resonances. Moreover, the magnitude of Kerr angle reaches to about 10 minutes at the azimuthal angle 45°, which is over 3 times of that of pure Co film. These phenomena are attributed to the SPP resonances with different diffraction orders of reciprocal lattice vectors.

Cost-utility analysis of different peg-interferon alpha-2b plus ribavirin treatment strategies as initial therapy for naïve Chinese patients with chronic hepatitis C.

BACKGROUND: Different peg-interferon alpha-2b plus ribavirin treatment strategies are more effective in treating hepatitis C. However, no cost-effectiveness data have been published using the clinical data from the peg-interferon alpha-2b and ribavirin in the treatment of patients with hepatitis C in Taiwan. AIM: To estimate the cost-effectiveness of different treatments with peg-interferon alpha-2b plus ribavirin for the initial treatment of patients with different genotype chronic hepatitis C. METHODS: Individual patient level data from a randomized clinical trial with peg-interferon plus ribavirin were applied to a Markov model to project lifelong clinical outcomes. Economic estimates and quality of life were based on published data and Taiwan patient data. We used a societal perspective and applied a 3% annual discount rate. RESULTS: Compared with different combination therapy strategies, peg-interferon alpha-2b plus weight-based dosing of ribavirin in all patients for 24 weeks is the most cost-effective treatment strategy. If the sustained virological response of peg-interferon plus ribavirin treatment for 48 weeks therapy in genotype 1 patients was higher than 67.8%, the best strategy of treating patients will be the peg-interferon plus weight-based dosing of ribavirin therapy for 48 weeks in genotype 1 patients and for 24 weeks in non-genotype 1 patients. CONCLUSIONS: Peg-interferon alpha-2b plus ribavirin combination for 24 weeks therapy in all genotype patients should reduce the incidence of liver complications, prolong life, improve quality of life and be cost-effective for the initial treatment of chronic hepatitis C.

Lipoprotein multigene families in Mycoplasma pneumoniae.

In this study, reverse transcriptase PCR was employed to construct a transcriptional profile of Mycoplasma pneumoniae lipoprotein genes contained in six multigene families. Most genes were found to be expressed. Many truncated lipoprotein genes were expressed, often polycistronically with other truncated genes, indicating that these genes may still be functional.

Chemical synthesis and magnetic properties of well-coupled FePt/Fe composite nanotubes.

A simple two-step hydrogen reduction method was used to synthesize FePt/Fe composite nanotubes. As the first step, L1(0) FePt nanotubes were prepared by heating a porous alumina template loaded with an alcohol solution of a Fe chloride and Pt chloride mixture in flowing hydrogen at 670 degrees C. Then, FePt/Fe composite nanotubes were obtained by reducing the alcohol solution of the Fe chloride within the formed FePt nanotubes at a lower temperature, namely 470 degrees C. Through changing the concentrations of initial alcohol solutions, the FePt:Fe atomic ratios of the composite nanotubes were easily adjusted and the magnetic properties were tuned accordingly. For (FePt)(100-x)/Fe(x) composite nanotubes with x ranging between 0 and 26 at.%, the hard and soft phases were well coupled and the coercivity was tunable over a large range (1.27-2.73 T). Furthermore, the marked interdiffusion between Fe and FePt, which usually exists in FePt-based composites fabricated by using conventional methods, was not observed in the formed composite nanotubes. This indicates the two-step hydrogen reduction method to be a promising route for synthesizing nanocomposites which are difficult to fabricate by using conventional methods due to the interdiffusion between different phases.

Mothers' perspectives on the quality of postpartum care in Central Shanghai, China.

OBJECTIVES: To investigate mothers' perspectives on the quality of postpartum care services in central Shanghai, China. DESIGN: Semi-structured interviews. SETTING: Two maternal and child health posts in two subdistricts in LW District, Central Shanghai, China. STUDY PARTICIPANTS: Fifty postpartum mothers who attended the maternal and child health posts in the two subdistricts in LW District, Central Shanghai, China. MAIN OUTCOME MEASURES: Mothers' perceived quality and adequacy of postpartum services. RESULTS: A majority of the mothers (90%; n = 45) were primiparas (first time mothers). Half did not consider the postpartum services to be of high quality. They defined high quality as 'full satisfaction of the mother and the child'. Their perception of quality was influenced by their concern about child care, an area in which they expressed the need for further improvement. CONCLUSION: Mothers indicated that to improve quality of services further, greater emphasis should be placed on: (1) health education on childcare; (2) more time allocation for discussion with health workers during their postpartum home visits so their questions and concerns could be addressed effectively; (3) access to health workers in times of need rather than during officially prescribed home visits; and (4) provision of continuous training for maternal and child health workers with respect to childcare. The findings will be relevant to health workers and policy makers involved in planning and implementation of maternal and child health services in similar urban settings in developing countries.

Effects of antecedent order and semantic context on Chinese pronoun resolution.

Three reading time experiments were conducted in order to examine the relative contributions of order of antecedents and semantic context to the resolution of temporarily ambiguous Chinese pronouns. These pronouns were ambiguous because each of them was preceded by two antecedents, both of which were likely candidates for coreference. The identity of the pronoun was revealed by subsequent disambiguating information that constrained the pronoun to one particular interpretation. Experiment 1 showed that reading of the disambiguating phrase was slower when the phrase confined the pronoun to the second rather than to the first antecedent. Experiment 2 produced the same effect of antecedent order (first vs. second antecedent) regardless of whether the target antecedent was an action-performing or an action-receiving entity. In Experiment 3, the order effect was eliminated by a biasing modifier inserted immediately before the pronoun. These results indicate that in a semantically neutral environment, the first-appearing antecedent is the preferred candidate for coreferencing the ambiguous Chinese pronoun. The interaction between order of antecedents and semantic context (in the form of preposed biasing modifiers) suggests that the initial comprehension of Chinese pronouns depends as much on contextual as on structural factors.

Role of flagellins from A and B loci in flagella formation of Halobacterium salinarum.

Haloarchaeal flagella are composed of a number of distinct flagellin proteins, specified by genes in two separate operons (A and B). The roles of these flagellins were assessed by studying mutants of H. salinarum with insertions in either the A or the B operon. Cells of the flgA- mutant produced abnormally short, curved flagella that were distributed all over the cell surface. The flgA2- strain produced straight flagella, mainly found at the poles. The flgB- mutant had flagella of the same size and spiral shape as wild-type cells, but these cells also showed unusual outgrowths, which appeared to be sacs filled with basal body-like structures. In broth cultures of this mutant, the medium accumulated flagella with basal body-like structures at their ends.

Drug prescribing in rural health facilities in China: implications for service quality and cost.

Overuse of drugs in rural areas of China has led to a growing concern regarding service quality and cost. The study found evidence of high levels of drug use in some rural health facilities in comparison with a number of other developing countries. Such a result was significantly associated with the government policy of financing health care, regulation and monitoring of health services, and users' attitudes and behaviour. It underlines the need for measures to be taken in China to improve drug use in order to allow its population access to effective care at reasonable cost.

PIP: Excessive and inappropriate drug prescribing practices in developing countries expose patients to health risks and raise health costs. In China, the transition to a market-oriented economy has been accompanied by a largely unregulated market for drugs and drug sales represent a major source of income for rural health services. This study examined drug prescribing patterns in 3 poor rural counties in China: Donglan (Guangxi province), Shibing (Guizhou province), and Xunyi (Shaanxi province). For each month in 1993, 100 outpatient records were randomly selected from each county hospital and 50 from each health center for review. A total of 7182 prescriptions (generally for 2-3 drugs) were issued. Between one-third and one-half of all prescriptions were for antibiotics. County health bureaus do not monitor the performance of health workers in relation to drugs unless a medical accident occurs. The income of health workers is directly related to the volume of drugs they sell--a factor that, along with patient equation of drug treatment with effective care, reinforces rampant overprescription. The average cost per prescription in township health centers was equal to 5.6, 2.2, and 6.2 times the average per capita daily income in Donglan, Shibing, and Xunyi, respectively. The mark up at health facility pharmacies was 15% for Western drugs and 20% for Chinese drugs and herbs. These findings indicate an urgent need for policies to end financial incentives for health workers to prescribe drugs, limit the right to prescribe or sell drugs to those with well-defined medical training, and ensure access to effective care at a reasonable cost.

Nanoscale characterization of gold colloid monolayers: a comparison of four techniques.

Atomic force microscopy (AFM), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and near-field scanning optical microscopy (NSOM) have been used to characterize the nanostructure of Au colloid-based surfaces. Because these substrates are composed of particles whose dimensions are known prior to assembly, they are well-suited for a critical comparison of the capabilities and limitations of each nanoscale imaging technique. The three criteria for this comparison, which are relevant to the field of nanoparticle assemblies in general, are (i) accuracy in establishing particle size, particle coverage, and interparticle spacing; (ii) accuracy in delineating surface topography; and (iii) ease of sample preparation, data acquisition, and image analysis. For colloidal Au arrays, TEM gives the most reliable size and spacing information but exhibits the greatest constraints with regard to sample preparation; in contrast, AFM is widely applicable but yields data that are the least straightforward to interpret. For accurate information regarding nanometer-scale architecture of particle-based surfaces, a combination of at least one scanning probe method (AFM, NSOM) and one accelerated-electron method (TEM, FE-SEM) is required.

Bringing basic health care to the rural poor.

In the 1960s and 1970s China provided a good model for financing and delivering rural health services in developing countries. Since the implementation of economic reforms which began in the 1980s, however, health services in poor areas have been showing signs of declining, with fewer people able to pay for the services they need. This article examines major problems of access to basic health care faced by the poor, and proposes a strategy for improving health service delivery in the poor areas.

PIP: From the 1950s to the 1970s, the health status of the Chinese improved significantly despite the developing national economy and low household incomes. Health gains were realized because rural health care had strong political support. Peasants were generally granted ready access to health care irrespective of their ability to pay. Now people referred to hospitals, even in emergencies, must pay a deposit before being admitted to the hospital. Many cannot afford the fees and therefore fail to receive medical care. The authors examine major problems of access to basic health care faced by the poor and propose a strategy for improving health service delivery in poor areas. Financial problems in villages and townships are discussed, followed by a 7-point strategy to finance rural health services comprised of the following approaches: rebuilding village health stations, strengthening township health centers, defining the basic service package to be covered by the plan, determining the cost of services, exploring potential sources of finance, changing the payment system for health care providers, and improving organization and management.

The financing and organization of health services in poor rural China: a case study in Donglan County.

The socio-economic reforms launched in China in the late 1970s led to rapid economic growth and, with it, health sector resources expanded rapidly. The rural health services have benefited from the policies of economic reform, but not in an optimal way, particularly in poor areas. This article uses a case study of a poor county--Donglan--to illustrate that the fiscal decentralization combined with the financial responsibility system have resulted in a weakening of financing and provision of rural health services in poor areas. The need for health facilities to generate revenue has had unfortunate consequences for the style of medical care, such as over-prescription. In addition, the collapse of the cooperative medical system and the weakening of the three-tier network of rural health care in Donglan have jeopardized preventive programs and threaten access to basic health care for the peasants, especially the poor. The study found evidence that preventive programs have deteriorated over the past years, the poor had financial difficulty in access to services, particularly hospital care, health facilities at township and village levels have been run down, and less training and supervision have been provided by upper-level health facilities. The article concludes with recommendations for a strategy for rebuilding and strengthening the three-tier network of rural health care, and for establishing a cooperative medical and health care scheme to ensure that the majority of peasants in Donglan can be guaranteed access to basic health services. Limited health resources will therefore be better used.

Trichomonas vaginalis and cervical cancer. A prospective study in China.

The relationship between Trichomonas vaginalis infection and cervical cancer was investigated prospectively in a cohort of 16,797 women aged 25 years or more who were followed from 1974 to 1985 within the framework of a cervical screening program in Jingan, China. Personal interviews were conducted by trained interviewers when the women first entered the screening program. At initial screening, 421 (2.51%) women had a positive cytologic diagnosis of T. vaginalis infection. Ninety-nine incident cases of pathologically confirmed squamous cell carcinoma were identified from the cohort, with a total of 140,018 person-years of observation. T. vaginalis infection was found to contribute to the risk of cervical cancer, as determined by crude estimates and after adjustment for potential confounding effects. In a multiple proportional hazards model, the relative risk for cervical cancer was 3.3 (95% confidence interval: 1.5 to 7.4) among women with T. vaginalis infection. Furthermore, in the multivariate analysis, increased risk of cervical cancer was associated with the following factors: number of extramarital sexual partners of both the subjects and their spouses, cigarette smoking, and irregular menstruation. Having a large number of negative Pap smears was associated with lower risk. This study suggests that there might be an association between T. vaginalis infection and the risk of cervical cancer, but only 4 to 5% of cervical cancer in Chinese women may be attributable to T. vaginalis infection.

New internal structure of spider dragline silk revealed by atomic force microscopy.

Atomic force microscopy was used to study the three-dimensional nanometer-scale structure of the dragline silk of Nephila clavipes from microtomed sections of the silk. Contrary to a previously proposed model of randomly distributed protein crystallites interspersed in amorphous regions, a highly organized skin-core structure of the fiber was observed. The skin appeared to be thin with no discernible distinct features. The core consists of pleated fibril-like structures, which are arranged in two concentric cylinders. Upon stretching, the pleats were smoothed out substantially. The mechanical properties of spider silk can quite straightforwardly be related to the newly observed structures.