Efficacy and tolerability of lercanidipine in mild to moderate hypertension among Asians of different ethnic groups.

Introduction: Calcium channel blockers are well established modalities for the treatment of hypertension. However, in spite of the availability of many efficacious agents, hypertension control continues to be poor. One reason is poor tolerability due to adverse events. Racial differences also exist. Lercanidipine, a third-generation calcium channel blocker, is associated with better tolerability. However, it has not been studied in the Asian population. This study examines its efficacy and tolerability in Asian subjects of different ethnicities. Methods: This was an eight-week open label study of adults with mild to moderate hypertension. Blood pressure (BP), pulse rate, self-administered symptom check and laboratory evaluations were done at baseline. Patients were prescribed 10 mg lercanidipine, with up-titration to 20 mg if BP was not controlled at Week 4. Baseline evaluations were repeated at Week 8. Adverse events were also enumerated. Results: 27 patients (mean age 53.4 +/- 12.1 years) completed the study. The baseline systolic BP (SBP), diastolic BP (DBP) and heart rate was 159 +/- 12.2, 96.6 +/- 7.7 mmHg and 71 +/- 13/min, respectively. Three racial groups were represented. SBP and DBP decreased significantly after four weeks of therapy. A further reduction to 139 +/- 14.3 and 88 +/- 9.8 (p-value is less than 0.0001) was seen in Week 8. The absolute SBP and DBP reduction was 20.5 mmHg (95 percent confidence interval [CI] 16.5-24.5, p-value is less than 0.0001) and 9.3 mmHg (95 percent CI 6.2-12.5, p-value is less than 0.0001), respectively. All adverse symptoms, except for palpitations, were reduced at the end of the study. Conclusion: Lercanidipine is efficacious and well tolerated in Asians of different ethnicities. Its BP lowering effects and tolerability in Asians appear to be similar to other studies on Caucasians and other calcium channel blockers

Evaluating the health-related quality of life of the rare disease population in Hong Kong using EQ-5D 3-level

Objectives This study aimed to establish a normative profile of health-related quality of life (HRQOL) of the rare disease (RD) population in Hong Kong (HK) and identify potential predictors. Methods Between March 2020 and October 2020, patients with RD and caregivers were recruited through Rare Disease Hong Kong, the largest RD patient group alliance in HK. HRQOL was derived using the EQ-5D 3-Level with reference to the established HK value set. Utility scores were stratified according to demographics and disease-related information. Multiple linear regression was performed to explore the associations between patient characteristics and HRQOL. Results A total of 286 patients, covering 107 unique RDs, reported a mean utility score of 0.53 (SD 0.36). Thirty patients (10.5%) reported negative utility scores, indicating worse-than-death health states. More problems were recorded in the “usual activities” and “self-care” dimensions. Univariate analyses revealed that neurologic diseases, high out-of-pocket expenditure, home modification, and living in public housing or subdivided flats/units were significantly associated with lower HRQOL. A total of 99 caregivers reported a mean utility score of 0.78 (SD 0.17), which was significantly associated with the utility score of patients they took care of (r = 0.32; P = .001). Conclusions The normative profile of the RD population was established, which revealed lower HRQOL in the RD population than other chronic disease groups and general population in HK. Findings were corroborated by evidence from other cohorts using EQ-5D, combined as part of a meta-analysis. Identifying predictors highlight areas that should be prioritized to improve HRQOL of RD population through clinical and psychosocial dimensions

Normal Cones and Thompson Metric

The aim of this paper is to study the basic properties of the Thompson metric $d_T$ in the general case of a real linear space $X$ ordered by a cone $K$. We show that $d_T$ has monotonicity properties which make it compatible with the linear structure. We also prove several convexity properties of $d_T$ and some results concerning the topology of $d_T$, including a brief study of the $d_T$-convergence of monotone sequences. It is shown most of the results are true without any assumption of an Archimedean-type property for $K$. One considers various completeness properties and one studies the relations between them. Since $d_T$ is defined in the context of a generic ordered linear space, with no need of an underlying topological structure, one expects to express its completeness in terms of properties of the ordering, with respect to the linear structure. This is done in this paper and, to the best of our knowledge, this has not been done yet. The Thompson metric $d_T$ and order-unit (semi)norms $|\cdot|_u$ are strongly related and share important properties, as both are defined in terms of the ordered linear structure. Although $d_T$ and $|\cdot|_u$ are only topological (and not metrical) equivalent on $K_u$, we prove that the completeness is a common feature. One proves the completeness of the Thompson metric on a sequentially complete normal cone in a locally convex space. At the end of the paper, it is shown that, in the case of a Banach space, the normality of the cone is also necessary for the completeness of the Thompson metric.Comment: 36 page

The combined role of MRI prostate and prostate health index in improving detection of significant prostate cancer in a screening population of Chinese men

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml -1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml -1. A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml -1 and PHI ≥35, or PSA 10.0-50.0 ng ml -1. Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml -1. Among 194 men with PSA 4.0-50.0 ng ml -1, 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml -1, additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml -1, and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI &lt;35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml -1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml -1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening.</p

The research results of charter companies in Croatia

Demand for Croatia as a nautical country constantly maintains the upward trend. The reason for this is the fact that Croatia is on the way to the EU integration as a future equal member state. This fact significantly contributes to Croatia’s openness to the generating market in both economical and in terms of tourism. Nautical tourism of Croatia is profitable which has been recognized by foreign entrepreneurs by directing their fleets to the Adriatic and developing successful and today frequently leading charter companies. The paper defines the charter activity and points out its characteristics. The purpose of the paper is to research, understand and set forth the attitudes of nautical tourists within the charter domain as an activity with the highest annual growth rate in nautical tourism. Methodology used in this paper was questionnaire based on three sections of questions. First section of questions refers to structure of charter companies, the second section of questions refers to the features of demand and season of 2009, and the third section of the questionnaire shows the expectations of charter companies for the season of 2010. Further on, the authors have additionally researched Slovenian charter companies and made the correlation of Slovenian and Croatian charter market.The research in this paper is descriptive, conducted on a one-time basis and on an intentionally selected sample. Based on the results, appropriate conclusions and attitudes have been made also incorporating specific views regarding the quality improvement of a nautical tourist product and charter offer

The Utility of High-Resolution Melting Analysis of SNP Nucleated PCR Amplicons—An MLST Based Staphylococcus aureus Typing Scheme

High resolution melting (HRM) analysis is gaining prominence as a method for discriminating DNA sequence variants. Its advantage is that it is performed in a real-time PCR device, and the PCR amplification and HRM analysis are closed tube, and effectively single step. We have developed an HRM-based method for Staphylococcus aureus genotyping. Eight single nucleotide polymorphisms (SNPs) were derived from the S. aureus multi-locus sequence typing (MLST) database on the basis of maximized Simpson's Index of Diversity. Only G↔A, G↔T, C↔A, C↔T SNPs were considered for inclusion, to facilitate allele discrimination by HRM. In silico experiments revealed that DNA fragments incorporating the SNPs give much higher resolving power than randomly selected fragments. It was shown that the predicted optimum fragment size for HRM analysis was 200 bp, and that other SNPs within the fragments contribute to the resolving power. Six DNA fragments ranging from 83 bp to 219 bp, incorporating the resolution optimized SNPs were designed. HRM analysis of these fragments using 94 diverse S. aureus isolates of known sequence type or clonal complex (CC) revealed that sequence variants are resolved largely in accordance with G+C content. A combination of experimental results and in silico prediction indicates that HRM analysis resolves S. aureus into 268 “melt types” (MelTs), and provides a Simpson's Index of Diversity of 0.978 with respect to MLST. There is a high concordance between HRM analysis and the MLST defined CCs. We have generated a Microsoft Excel key which facilitates data interpretation and translation between MelT and MLST data. The potential of this approach for genotyping other bacterial pathogens was investigated using a computerized approach to estimate the densities of SNPs with unlinked allelic states. The MLST databases for all species tested contained abundant unlinked SNPs, thus suggesting that high resolving power is not dependent upon large numbers of SNPs

A Very Early-Branching Staphylococcus aureus Lineage Lacking the Carotenoid Pigment Staphyloxanthin

Here we discuss the evolution of the northern Australian Staphylococcus aureus isolate MSHR1132 genome. MSHR1132 belongs to the divergent clonal complex 75 lineage. The average nucleotide divergence between orthologous genes in MSHR1132 and typical S. aureus is approximately sevenfold greater than the maximum divergence observed in this species to date. MSHR1132 has a small accessory genome, which includes the well-characterized genomic islands, νSAα and νSaβ, suggesting that these elements were acquired well before the expansion of the typical S. aureus population. Other mobile elements show mosaic structure (the prophage φSa3) or evidence of recent acquisition from a typical S. aureus lineage (SCCmec, ICE6013 and plasmid pMSHR1132). There are two differences in gene repertoire compared with typical S. aureus that may be significant clues as to the genetic basis underlying the successful emergence of S. aureus as a pathogen. First, MSHR1132 lacks the genes for production of staphyloxanthin, the carotenoid pigment that confers upon S. aureus its characteristic golden color and protects against oxidative stress. The lack of pigment was demonstrated in 126 of 126 CC75 isolates. Second, a mobile clustered regularly interspaced short palindromic repeat (CRISPR) element is inserted into orfX of MSHR1132. Although common in other staphylococcal species, these elements are very rare within S. aureus and may impact accessory genome acquisition. The CRISPR spacer sequences reveal a history of attempted invasion by known S. aureus mobile elements. There is a case for the creation of a new taxon to accommodate this and related isolates

Adenovirus-Associated Virus Vector-Mediated Gene Transfer in Hemophilia B

NIHR (RP-PG-0310-1001), the Medical Research Council, the Katharine Dormandy Trust, the U.K. Department of Health, NHS Blood and Transplant, the NIHR Biomedical Research Centers (to University College London Hospital and University College London), the ASSISI Foundation of Memphis, the American Lebanese Syrian Associated Charities, the Howard Hughes Medical Institute, the National Heart, Lung, and Blood Institute (HL094396), the Royal Free Hospital Charity Special Trustees Fund 35, the Royal Free Hospital NHS Trust, and St. Jude Children’s Research Hospita