Comorbidity Burden and Treatment Patterns of Psoriasis in Vietnam: Real-World Data from the EXPAND Study.

INTRODUCTION: Psoriasis is a multi-faceted, immune-mediated inflammatory disease associated with a wide range of comorbidities. Real-world data on treatment patterns, comorbidities, and economic burden in patients with psoriasis are needed for comprehensive patient care in Vietnam. METHODS: A retrospective chart review study was conducted using secondary data extracted from patients' medical records of two hospitals in Vietnam, with the aim of identifying adult patients with a confirmed diagnosis of psoriasis. The index date was defined as the date of first diagnosis between 1 January 2020 and 31 October 2021. Sociodemographic factors, disease characteristics, comorbidities, medication usage, drug survival, and medication costs were analyzed. RESULTS: A total of 661 patients were identified (mean ± standard deviation [SD] age 43.5 ± 14.8 years). The most prevalent comorbidity was dyslipidemia (49.6% of patients), followed by hypertension (23.4%), and psoriatic arthritis (10.4%). In total, 44% of patients received biologic therapies. Overall, 66.7% and 54.3% of patients receiving biologic and non-biologic therapies, respectively, had ≥ 1 comorbidity. Only 23.2% of patients with psoriasis-related comorbidities stopped therapy with biologics. Biologics had a longer retention time (17.0 months) than non-biologics (6.0 months) in patients with comorbidities. Patients with comorbidities had significantly higher total annual healthcare costs than those without comorbidities (in US dollars: USD901 vs. USD304; p < 0.001), mainly due to the relatively higher costs associated with the use of biologics. CONCLUSION: Patients with psoriasis in Vietnam experience a high disease and economic burden due to comorbidities. Evidence from this real-world study supports the need for routine monitoring of and an appropriate treatment course for psoriasis-related comorbidities.

Effectiveness of thirteen-valent pneumococcal conjugate vaccine to prevent serotype 3 invasive pneumococcal disease in Quebec in children, Canada.

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7 was replaced by PCV10 in 2009, by PCV13 in 2011 and by PCV10 in 2018, without catch-up in all instances. The objective was to estimate PCV13 effectiveness to prevent serotype 3 invasive pneumococcal disease in children aged less than 5 years, using 2010-2018 mandatory notification and laboratory surveillance data, an indirect cohort design and multivariate logistic regression models. A total of 29 cases of serotype 3 and 290 non-vaccine serotype cases as controls were analysed. Overall vaccine effectiveness (≥1 dose) was estimated at 59% [-39% to 88%]. During the first year after the last dose effectivness was 88% [47% to 97%] whereas no protection was observed thereafter. There was no trend towards increased effectiveness with the number of doses. PCV13 protection against serotype 3 IPD seems to be short-lived.

Long-Term Effectiveness and Drug Survival of Secukinumab in Vietnamese Patients with Psoriasis: Results from a Retrospective ENHANCE Study.

INTRODUCTION: Psoriasis (PsO), an immune-mediated inflammatory skin disorder, has substantial negative impact on patients' quality of life. Secukinumab, an approved treatment for moderate-to-severe plaque PsO, has an established long-term efficacy and safety profile. This study aims to provide real-world evidence of long-term effectiveness and retention rate of secukinumab in Vietnamese patients with PsO. METHODS: This retrospective, observational study collected medical records of adult patients with moderate-to-severe PsO receiving secukinumab treatment from Ho Chi Minh City Hospital of Dermato-Venereology. The primary objective was to evaluate secukinumab effectiveness in PsO as measured by 75% improvement in psoriasis area and severity index (PASI 75) at month 12. Secondary objectives were PASI 90/100, absolute PASI ≤ 3 and ≤ 5, Dermatology Life Quality Index (DLQI), and retention rate over 48 months. RESULTS: In total, 232 patients with moderate-to-severe PsO met inclusion criteria; 68.1% were male, with median age and age of onset of 39 and 27.5 years, respectively. Median time from onset of PsO to secukinumab treatment was 120 months, 95.3% were prior biologics/disease-modifying antirheumatic drugs naive and 41.4% received concomitant therapies for PsO; 82.3% had national insurance coverage. At month 12, 93.9% of patients achieved PASI 75 (primary endpoint); 80.2/56.9% achieved PASI 90/100; 91.4 and 84.8% patients achieved absolute PASI ≤ 5 and ≤ 3, respectively. The response was sustained over 48 months, with 91.9%/78.0%/52.0% of patients achieving PASI 75/90/100, 89.5% and 82.1% patients achieving absolute PASI ≤ 5 and ≤ 3, respectively. At month 12, 61.4% of patients achieved DLQI 0/1 which was sustained up to month 48 (69.2%). Secukinumab adherence rate of 84.9% at month 12 dropped to 34.2% at month 48. Patients receiving concomitant therapy and national insurance showed higher adherence rate. CONCLUSION: Secukinumab demonstrated long-term effectiveness in real-world Vietnamese patients with moderate-to-severe PsO, with treatment adherence being higher in patients having concomitant therapies and national insurance.

Effective Fragment Potentials for Flexible Molecules: Transferability of Parameters and Amino Acid Database.

An accurate but efficient description of noncovalent interactions is a key to predictive modeling of biological and materials systems. The effective fragment potential (EFP) is an ab initio-based force field that provides a physically meaningful decomposition of noncovalent interactions of a molecular system into Coulomb, polarization, dispersion, and exchange-repulsion components. An EFP simulation protocol consists of two steps, preparing parameters for molecular fragments by a series of ab initio calculations on each individual fragment, and calculation of interaction energy and properties of a total molecular system based on the prepared parameters. As the fragment parameters (distributed multipoles, polarizabilities, localized wave function, etc.) depend on a fragment geometry, straightforward application of the EFP method requires recomputing parameters of each fragment if its geometry changes, for example, during thermal fluctuations of a molecular system. Thus, recomputing fragment parameters can easily become both computational and human bottlenecks and lead to a loss of efficiency of a simulation protocol. An alternative approach, in which fragment parameters are adjusted to different fragment geometries, referred to as "flexible EFP", is explored here. The parameter adjustment is based on translations and rotations of local coordinate frames associated with fragment atoms. The protocol is validated on extensive benchmark of amino acid dimers extracted from molecular dynamics snapshots of a cryptochrome protein. A parameter database for standard amino acids is developed to automate flexible EFP simulations in proteins. To demonstrate applicability of flexible EFP in large-scale protein simulations, binding energies and vertical electron ionization and electron attachment energies of a lumiflavin chromophore of the cryptochrome protein are computed. The results obtained with flexible EFP are in a close agreement with the standard EFP procedure but provide a significant reduction in computational cost.

Oligogenic inheritance of a human heart disease involving a genetic modifier.

Complex genetic mechanisms are thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human cardiac anomaly can be caused by a combination of rare, inherited heterozygous mutations. Whole-exome sequencing of a nuclear family revealed that three offspring with childhood-onset cardiomyopathy had inherited three missense single-nucleotide variants in the MKL2, MYH7, and NKX2-5 genes. The MYH7 and MKL2 variants were inherited from the affected, asymptomatic father and the rare NKX2-5 variant (minor allele frequency, 0.0012) from the unaffected mother. We used CRISPR-Cas9 to generate mice encoding the orthologous variants and found that compound heterozygosity for all three variants recapitulated the human disease phenotype. Analysis of murine hearts and human induced pluripotent stem cell-derived cardiomyocytes provided histologic and molecular evidence for the NKX2-5 variant's contribution as a genetic modifier.

Comparison of Initial Pediatric Outpatient Echocardiogram Indications between Community and Academic Practice.

OBJECTIVE: To compare the appropriateness and diagnostic yield of initial outpatient transthoracic echocardiography (TTE) between a community pediatric cardiology practice and an academic children's hospital. STUDY DESIGN: Initial outpatient pediatric TTE ordered by pediatric cardiologists between January and March 2014 at a community practice (Packard Children's Health Alliance [PCHA]; n = 238) and an academic tertiary center (Lucile Packard Children's Hospital [LPCH]; n = 76) were evaluated based on appropriate use criteria (AUC) released in December 2014. Multivariate logistic regression was used to identify predictors of "rarely appropriate" indications and abnormal TTE findings. RESULTS: Of 314 TTEs, 165 (52.5%) were classified as "appropriate," 40 (12.7%) were classified as "may be appropriate," 100 (31.9%) were classified as "rarely appropriate," and 9 (2.9%) were unclassifiable. The proportion of abnormal findings did not differ between the 2 practice settings (5.3% for LPCH vs 7.6% for PCHA; P = .61). TTEs performed at PCHA were significantly more likely to be "rarely appropriate" (OR, 2.57; 95% CI, 1.28-5.15; P = .008). Children aged <1 year (OR, 1.90; 95% CI, 1.03-3.50; P = .04) and ordering providers with <10 years since the completion of their fellowship (OR, 2.15; 95% CI, 1.20-3.87; P = .01) were associated with "rarely appropriate" indications. "Appropriate" TTEs were associated with abnormal findings (OR, 8.69; 95% CI, 1.77-42.68; P = .008). CONCLUSION: The community practice was independently associated with greater inappropriate ordering of initial outpatient pediatric TTEs compared with the academic practice. The assessment of practice patterns following AUC release should account for physician and practice-related factors that could influence differences in TTE ordering patterns.

The changing landscape of travel health services in Canada.

Canadians are increasingly travelling to areas that would necessitate a pre-travel consultation. Changes in professional regulations in Canada allow greater autonomy of nurses and pharmacists, resulting in shifts in provision of travel health services. We surveyed 824 Canadian travel clinics, 270 (33%) of whom responded. Private clinics were most common, and more likely to offer extended hours and drop-in appointments. In one province, pharmacies dominated. Half the services were relatively new and a similar proportion saw fewer than 10 patients weekly; 1/3 had a single provider. The increased spectrum of services may increase convenience for travellers but the large proportion seeing low numbers of clients will challenge providers to maintain competence.

Prominent coronary artery flow with normal coronary artery anatomy is a rare but ominous harbinger of poor outcome in the fetus.

OBJECTIVES: "Heart sparing" refers to prominent antegrade fetal coronary artery (CA) blood flow readily visualized by color Doppler and is a harbinger of poor outcome in growth restricted fetus, but little is known of the features and presentation of heart sparing in normally grown fetuses. Our objective was to describe heart sparing effects in normally grown fetuses, and compare the presentation and outcome of heart sparing between fetuses with growth restriction and those who were normally grown. METHODS: In a series of fetuses with prominent antegrade CA flow, we assessed Doppler flow profiles in the aortic isthmus, ductus venosus (DV), umbilical vein (UV), umbilical artery (UA) and middle cerebral artery (MCA). We calculated MCA and UA systolic/diastolic ratios and the cerebral placental ratio, and measured fetal biometry. We evaluated cardiac function using the myocardial performance index (MPI) and the cardiovascular profile score (CVPS). RESULTS: Ten fetuses with heart sparing had normal DV flow at 24-36.6 (mean 30.9) weeks of gestation. Five had growth restriction (Group 1); 4/5 had normal MPI and CVPS, and one died. Five were normally grown (Group 2); 5/5 had elevated MPI and decreased CVPS, of these 2 died in utero and one died immediately after birth despite urgent delivery. Coronary arteries were normal after birth or autopsy. CONCLUSIONS: Heart sparing confers a poor prognosis in fetal growth restriction and in normally grown fetuses with cardiac dysfunction. We suggest CA flow be assessed in all high-risk fetuses.

Changes in the Composition of Aromatherapeutic Citrus Oils during Evaporation.

The composition of some commercial Citrus oils, lemon, sweet orange, and tangerine, designated for aromatherapy, was examined before and after partial evaporation in a stream of nitrogen. The intact oils contained the expected mixtures of mono- and sesquiterpenes, with hydrocarbons dominating and lesser amounts of oxygenated analogues making up the remainder. Gas chromatography-mass spectrometry was used to follow alterations in the relative amounts of the various components present as evaporation proceeded. Changes were marked, and in particular more volatile components present in the intact oils rapidly disappeared. Thus the balance of content was shifted away from monoterpene hydrocarbons towards the analogous alcohols and carbonyl compounds. The results of this differential evaporation are discussed and possible consequences for aromatherapy use are noted. The case of lemon oil was especially interesting as the relative amount of citral, a known sensitizer, remaining as time elapsed represented an increasing percentage of the total oil.

Travel-related shigellosis in Quebec, Canada: an analysis of risk factors.

BACKGROUND: Travel-related shigellosis is not well documented in Canada although it is frequently acquired abroad and can cause severe disease. OBJECTIVES: To describe the epidemiology of travel-related cases of shigellosis for Quebec (Canada) and to identify high-risk groups of travelers. METHOD AND DATA SOURCES: We performed a random sampling of 335 shigellosis cases (from a total of 760 cases) reported in the provincial database of reportable diseases from January 1, 2004, to December 31, 2007. Each case was analyzed according to information available in the epidemiology questionnaire. Total number of trips by region from Statistics Canada was used as denominator to estimate the risk according to region of travel. RESULTS: Annually, between 43 and 54% of the shigellosis cases were reported in travelers, 45% of whom were aged between 20 and 44 years. Children under 11 years accounted for nearly 16% of cases, but represent only 4% of travelers. Most cases in travelers were serogroups Shigella sonnei (50%) or Shigella flexneri (45%). Almost 31% of cases were reported between January and March. The majority (64%) were acquired in Central America, Mexico, or the Caribbean. However, the Indian subcontinent, Africa, and South America had the highest ratio of number of cases per number of trips. Tourists represented 76% of the cases; 62% of them had traveled for <2 weeks. At least 15% of cases among travelers were hospitalized. CONCLUSIONS: In Quebec, travel-related cases of shigellosis represent a large burden of total cases. Short-term travelers are at risk, as well as young children. The majority of cases occur in the winter months, corresponding to the peak of travel to "sunshine destinations." Continuous efforts should be made to encourage all travelers to seek pre-travel care, and to inform primary care practitioners of health risks faced by their patients abroad, even for those going to resorts.

Tissue Doppler is more sensitive and reproducible than spectral pulsed-wave Doppler for fetal right ventricle myocardial performance index determination in normal and diabetic pregnancies.

BACKGROUND: The aim of this study was to compare the reproducibility, agreement, and sensitivity of pulsed-wave Doppler tissue imaging (DTI) versus spectral Doppler assessment of right ventricular (RV) myocardial performance index (MPI) in midgestation fetuses in both a normal and a disease state. METHODS: RV MPI was calculated using pulsed-wave DTI and spectral Doppler in normal pregnancies (n = 69) and in women with pregestational diabetes (n = 51). Intraobserver and interobserver variability and agreement were evaluated using Bland-Altman analysis. Student's t tests were used for comparisons of differences. RESULTS: In normal fetuses, RV MPI derived by the two methods showed no statistical difference, were interchangeable (DTI, 0.51 ± 0.10; spectral Doppler, 0.50 ± 0.12; P = .686), and were in agreement by Bland-Altman analysis. However, in fetuses of mothers with diabetes, the two methods produced different RV MPI measurements (DTI, 0.56 ± 0.10; spectral Doppler, 0.51 ± 0.12; P < .001). Intraobserver and interobserver bias was lower for DTI. CONCLUSIONS: The DTI method of measuring fetal RV MPI is more sensitive, has less variability and more precision, and is better able to demonstrate subtle abnormalities in cardiac function than the spectral Doppler method in diabetic versus normal pregnancies.

Cases of malaria, hepatitis A, and typhoid fever among VFRs, Quebec (Canada).

BACKGROUND: Visiting friends and relatives (VFRs), especially young VFRs, are increasingly recognized in the industrialized world as a high-risk group of travelers. METHODS: We performed a descriptive, cross-sectional design study of cases of malaria, hepatitis A, and typhoid reported to the Quebec registry of notifiable diseases between January 2004 and December 2007, occurring in VFRs and non-VFRs travelers. RESULTS: VFRs account for 52.9% of malaria cases, 56.9% of hepatitis A cases, and 94.4% of typhoid cases reported in Quebec travelers. Almost all (91.6%) of the malaria cases among VFRs were acquired in Africa, particularly in sub-Saharan Africa. An important proportion of malaria cases among VFRs (86.4%) were due to Plasmodium falciparum. The vast majority (76.6%) of typhoid fever cases among VFRs were reported by travelers who had visited the Indian subcontinent. Among VFRs, 40% of total cases were under 20 y of age, compared to less than 6% among non-VFRs. Those under 20 years of age also accounted for 16.9% of malaria cases, 50% of typhoid cases, and 65.2% of hepatitis A cases among VFRs. CONCLUSION: Our study clearly shows that VFR children should be a primary target group for pre-travel preventive measures.

Danon disease with typical early-onset cardiomyopathy in a male: focus on a novel LAMP-2 mutation.

We report a case of a 16-yr-old male with Danon disease caused by a novel mutation in the LAMP-2 gene. Mutations in the LAMP-2 gene result in the absence of LAMP-2 on immunohistochemical staining of muscle tissue, thus defining Danon disease, a rare X-linked myopathy. It is characterized clinically by HCM or left ventricular hypertrophy, a WPW pattern on ECG, variable degrees of muscular weakness (skeletal myopathy), mental retardation, and retinal changes. The patient presented with severe skeletal muscular weakness and respiratory failure. He also had a history of two OHTs, the first one for severe HCM and the second for allograft rejection. The patient's myopathy was initially presumed to be exclusively related to steroid-induced "critical care myopathy." However, further evaluation with a thigh muscle biopsy revealed autophagic vacuoles with sarcolemnal features suggestive of a lysosomal storage disorder. DNA analysis ultimately identified a previously unreported hemizygous IVS6+3_+6delGAGT splice site deletion mutation in the LAMP-2 gene located within the 5' splice site of intron 6, consistent with Danon disease.

Hepatitis A, typhoid and malaria among travelers--surveillance data from Québec (Canada).

Analysis of epidemiological data on health problems related to international travel helps put into perspective preventive interventions for travelers. To document the epidemiological context of travel health interventions in Québec, we reviewed surveillance data for three infectious diseases. The analysis included data collected in the notifiable diseases surveillance system for hepatitis A, typhoid, and malaria cases reported from 2000 to 2002. Additional data were obtained from the provincial hepatitis risk factor database as well as from regional public health departments. More than 40% of cases of hepatitis A for which risk factor information is available are associated with international travel; 20% of these cases were contracted in Mexico and 22% in the West Indies. The risk of acquiring hepatitis A seems to be higher among travelers under 35 years of age; also, given the number of Quebecers traveling to all regions of the world, this risk is proportionally higher in Africa. Data gathered for typhoid indicate that the risk to travelers from Québec is proportionately higher for Quebecers traveling to the Indian subcontinent and whose purpose is to visit family and friends, and for those who stay abroad for 4 weeks or longer. The risk of malaria is greater in Africa (where contracted cases are mostly caused by Plasmodium falciparum). Over half of malaria cases involve individuals traveling abroad for business (including volunteerism), and almost 75% contracted the disease during a stay of a month or more. Nearly half of the cases had not taken chemoprophylaxis. Available data have limitations for infectious disease surveillance among Québec travelers: imprecise number of cases (underdiagnosis and underreporting), imprecise denominators (number of travelers), and lack of data on the characteristics of trips taken. However, despite its limitations, this profile of infectious diseases among travelers from Québec provides interesting data for preventive intervention.

Travel clinics in Québec (Canada).

To continuously improve its assistance to Québec travel health providers, the Québec Advisory Committee on Travel Health conducted an exploratory and descriptive survey of dedicated travel clinics in Québec (Canada). During autumn 2003, a cross-sectional descriptive survey was carried out among the 97 travel health clinics listed in Québec. Data were collected using a self-administered questionnaire sent by mail. The response rate was 94%. More than three quarters of travel clinics in Québec are located in community health centers; the others are in private clinics and in hospitals. Although 80% of the clinics are located outside the most densely inhabited regions of Québec, they carry out less than 30% of the total number of pretravel consultations. Almost 60% of the clinics have fewer than 500 consultations a year. Overall, more than 114,000 travel health consultations are performed annually in Québec travel health clinics. Preventive services to travelers, including the most commonly used vaccines for travelers, are available in all regions of Québec, except in the northernmost region. Smaller clinics offer fewer services to travelers in terms of antimalarial prescriptions, less common vaccines, and post-travel consultations. The main sources of information for travel health practitioners are guidelines provided by public health authorities. Data obtained provide an up-to-date portrait of the services available in travel clinics in Québec that should assist public health authorities adapt their interventions to the needs and realities of these clinics.

Phospholipase Cepsilon regulates ovulation in Caenorhabditis elegans.

Phospholipase Cepsilon (PLCepsilon) is a novel class of phosphoinositide-specific PLC with unknown physiological functions. Here, we present the first genetic analysis of PLCepsilon in an intact organism, the nematode Caenorhabditis elegans. Ovulation in C. elegans is dependent on an inositol 1,4,5-trisphosphate (IP(3)) signaling pathway activated by the receptor tyrosine kinase LET-23. We generated deletion mutants of the gene, plc-1, encoding C. elegans PLCepsilon. We observed a novel ovulation phenotype whereby oocytes are trapped in the spermatheca due to delayed dilation of the spermatheca-uterine valve. The expression of plc-1 in the adult spermatheca is consistent with its involvement in regulation of ovulation. On the other hand, we failed to observe genetic interaction of plc-1 with let-23-mediated IP(3) signaling pathway genes, suggesting a complex mechanism for control of ovulation.

Caenorhabditis elegans inositol 5-phosphatase homolog negatively regulates inositol 1,4,5-triphosphate signaling in ovulation.

Ovulation in Caenorhabditis elegans requires inositol 1,4,5-triphosphate (IP(3)) signaling activated by the epidermal growth factor (EGF)-receptor homolog LET-23. We generated a deletion mutant of a type I 5-phosphatase, ipp-5, and found a novel ovulation phenotype whereby the spermatheca hyperextends to engulf two oocytes per ovulation cycle. The temporal and spatial expression of IPP-5 is consistent with its proposed inhibition of IP(3) signaling in the adult spermatheca. ipp-5 acts downstream of let-23, and interacts with let-23-mediated IP(3) signaling pathway genes. We infer that IPP-5 negatively regulates IP(3) signaling to ensure proper spermathecal contraction.