Effect of single versus grouped culture of human cumulus-oocyte complexes in PCOS women treated with biphasic in vitro maturation: A sibling oocyte pilot study.

Purpose: This study investigated the differences in the maturation rate of single versus grouped cumulus-oocyte complexes (COCs) culture methods for capacitation in vitro maturation (CAPA-IVM) in women with polycystic ovary syndrome (PCOS). Methods: This study was performed at My Duc Phu Nhuan Hospital, Vietnam from October 1, 2020 to October 24, 2021. Women aged 18-37 years with a diagnosis of PCOS were recruited. COCs from each woman were randomly divided into two groups: single or grouped culture during CAPA-IVM culture. The primary outcome was the maturation rate. Results: A total of 322 COCs from 15 eligible women included were randomly assigned to the two study groups. The maturation rate was comparable between the single and grouped culture groups (61.3% vs. 64.8%; p = 0.56). There were no significant differences in the number of 2-pronuclei fertilized oocytes, number of day-3 embryos, and number of good-quality embryos in the two culture method groups. In the single culture group, COCs morphology was associated with the day-3 embryo formation rate but not the maturation rate. Conclusions: Comparable oocyte maturation and embryology outcomes between single and grouped COCs culture utilizing sibling COCs derived from women with PCOS suggest the feasibility of both methods for CAPA-IVM culture.

A spectrum of viral diseases in Odisha state, eastern India: An evidence-based analysis from 2010-2017.

Introduction: Emerging and re-emerging viral diseases are a major threat to public health. Odisha, being one of the coastal states in the country, reports many viral illnesses due to its typical geographical location. This study focuses on the prevalence of different viral diseases in the state of Odisha, India, from 2010-2017. Material and Methods: A total of 43,397 patients with clinical suspicion of viral diseases were screened for different viral etiologies during 2010-2017. The laboratory diagnosis was conducted by serology (ELISA) and RT-PCR for 24 different viruses, i.e., dengue, chikungunya, Japanese encephalitis, hepatitis A virus, hepatitis E virus, hepatitis B virus, hepatitis C virus, rotavirus, herpes simplex virus-1 and herpes simplex virus-2, Epstein-Barr virus, cytomegalovirus, and respiratory viruses. Patients were enrolled from sporadic hospital admissions and outbreaks under different categories as per clinical diagnoses like fever with rash, diarrhoea, encephalitis, jaundice, respiratory illness, and fever of unknown etiology. Results: The majority of patients belonged to exanthematous group, i.e., fever with rash (32.24%). The number of males was more in all categories except fever with rash, where females (53.34%) were more. Children <16 years of age were found to be the predominant age group for suspected viral diarrhoea (85.26%), encephalitis (76.96%), fever of unknown origin (40.16%), and respiratory infections (27.23%). Conclusion: Not only vector-borne diseases pose a threat to the Odisha state, but other viral illnesses have also emerged. This detailed report of different viral diseases in the state of Odisha will support public health management.

Cumulative live birth rate after oocyte in vitro maturation with a pre-maturation step in women with polycystic ovary syndrome or high antral follicle count.

PURPOSE: This study evaluated the 24-month cumulative live birth rate (CLBR) for women with polycystic ovary syndrome (PCOS) or high antral follicle count (AFC) who underwent oocyte in vitro maturation (IVM) with pre-maturation step (CAPA-IVM). METHODS: This multicenter, retrospective study was performed at IVFMD, My Duc Hospital, and IVFMD Phu Nhuan, My Duc Phu Nhuan Hospital from 1 January 2017 to 31 December 2019. All women with PCOS or high AFC treated with a CAPA-IVM cycle were included. Cumulative live birth was defined as at least one live birth resulting from the initiated CAPA-IVM cycle. Where a woman did not return for embryo transfer, outcomes were followed up until 24 months from the day of oocyte aspiration. Logistic regression was performed to identify factors predicting the CLBR. RESULTS: Data from 374 women were analyzed, 368 of whom had embryos for transfer (98.4%), and six had no embryos for transfer (1.6%). The oocyte maturation rate was 63.2%. The median number of frozen embryos was 4 [quartile 1, 2; quartile 3, 6]. Cumulative clinical pregnancy and ongoing pregnancy rates were 60.4% and 43.6%, respectively. At 24 months after starting CAPA-IVM treatment, the CLBR was 38.5%. Multivariate analysis showed that patient age and number of frozen embryos were significant predictors of cumulative live birth after CAPA-IVM. CONCLUSIONS: CAPA-IVM could be considered as an alternative to in vitro fertilization for the management of infertility in women with PCOS or a high AFC who require assisted reproductive technology.

Antral follicle count and anti-Müllerian hormone to classify low-prognosis women under the POSEIDON criteria: a classification agreement study of over 9000 patients.

STUDY QUESTION: What is the agreement between antral follicle count (AFC) and anti-Müllerian hormone (AMH) levels when used to patient classification according to the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria? SUMMARY ANSWER: Our study indicates a strong agreement between the AFC and the AMH levels in classifying POSEIDON patients; thus, either can be used for this purpose, although one in four women will have discordant values when both biomarkers are used. WHAT IS KNOWN ALREADY: According to the POSEIDON criteria, both AFC and AMH may be used to classify low-prognosis patients. Proposed AFC and AMH thresholds of 5 and 1.2 ng/ml, respectively, have their basis in published literature; however, no study has yet determined the reproducibility of patient classification in comparing one biomarker with the other, nor have their thresholds ever been validated within this patient population. STUDY DESIGN, SIZE, DURATION: A population-based cohort study involving 9484 consecutive patients treated in three fertility clinics in Brazil, Turkey and Vietnam between 2015 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were infertile women between 22 and 46 years old in their first in vitro fertilization/intracytoplasmic sperm injection cycle of standard ovarian stimulation with exogenous gonadotropins whose baseline ovarian reserves had been assessed by both AFC and AMH. Details of pre- and post-treatment findings were input into a coded research file. Two indicators of interest were created to classify patients according to the POSEIDON criteria based upon AFC and AMH values. Patients who did not fit any of the four POSEIDON groups were classified as non-POSEIDON. AFC was determined in the early follicular phase using two-dimensional (2D) transvaginal ultrasonography, whereas AMH values were based on the modified Beckman Coulter generation II enzyme-linked immunosorbent assay. Agreement rates were computed between AFC and AMH to classify patients using Cohen's kappa statistics. Logistic regression analyzes were carried out to examine the association between ovarian markers and low (<4) and suboptimal (4-9) oocyte yield. MAIN RESULTS AND THE ROLE OF CHANCE: The degree of agreement in classifying patients according to POSEIDON groups was strong overall (kappa = 0.802; 95% CI: 0.792-0.811). A total of 73.8% of individuals were classified under the same group using both biomarkers. The disagreement rates were ∼26% and did not diverge when AFC or AMH was used as the primary biomarker criterion. Significant regression equations were found between ovarian markers and oocyte yield (P < 0.0001). For low oocyte yield, the optimal AFC and AMH cutoff values were 5 and 1.27 ng/ml with sensitivities of 0.61 and 0.66, specificities of 0.81 and 0.72, and AUC receiver operating characteristics of 0.791 and 0.751, respectively. For suboptimal oocyte yield respective AFC and AMH cutoffs were 12 and 2.97 ng/ml with sensitivities of 0.74 and 0.69, specificities of 0.76 and 0.66 and AUCs of 0.81 and 0.80. LIMITATIONS, REASONS FOR CAUTION: Our study relied on 2D transvaginal sonography to quantify the AFC and manual Gen II assay for AMH determination and classification of patients. AMH data must be interpreted in an assay-specific manner. Treatment protocols varied across centers potentially affecting patient classification. WIDER IMPLICATIONS OF THE FINDINGS: Three of four patients will be classified the same using either AFC or AMH values. Both biomarkers provide acceptable and equivalent accuracy in predicting oocyte yield further supporting their use and proposed thresholds in daily clinical practice for patient classification according to the POSEIDON criteria. However, the sensitivity of POSEIDON thresholds in predicting low oocyte yield is low. Clinicians should adopt the biomarker that may best reflect their clinical setting. STUDY FUNDING/COMPETING INTEREST(S): Unrestricted investigator-sponsored study grant (MS200059_0013) from Merck KGaA, Darmstadt, Germany. The funder had no role in study design, data collection, analysis, decision to publish or manuscript preparation. S.C.E. declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. H.Y. declares receipt of payment for lectures from Merck and Ferring. L.N.V. receives speaker fees and conferences from Merck, Merck Sharp and Dohme (MSD) and Ferring and research grants from MSD and Ferring. T.M.H. received speaker fees and conferences from Merck, MSD and Ferring. The remaining authors have nothing to disclose. TRIAL REGISTRATION NUMBER: not applicable.

Cumulative delivery rate per aspiration IVF/ICSI cycle in POSEIDON patients: a real-world evidence study of 9073 patients.

STUDY QUESTION: What is the cumulative delivery rate (CDR) per aspiration IVF/ICSI cycle in low-prognosis patients as defined by the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria? SUMMARY ANSWER: The CDR of POSEIDON patients was on average ∼50% lower than in normal responders and varied across POSEIDON groups; differences were primarily determined by female age, number of embryos obtained, number of embryo transfer (ET) cycles per patient, number of oocytes retrieved, duration of infertility, and BMI. WHAT IS KNOWN ALREADY: The POSEIDON criteria aim to underline differences related to a poor or suboptimal treatment outcome in terms of oocyte quality and quantity among patients undergoing IVF/ICSI, and thus, create more homogenous groups for the clinical management of infertility and research. POSEIDON patients are presumed to be at a higher risk of failing to achieve a live birth after IVF/ICSI treatment than normal responders with an adequate ovarian reserve. The CDR per initiated/aspiration cycle after the transfer of all fresh and frozen-thawed/warmed embryos has been suggested to be the critical endpoint that sets these groups apart. However, no multicenter study has yet substantiated the validity of the POSEIDON classification in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment using real-world data. STUDY DESIGN, SIZE, DURATION: Multicenter population-based retrospective cohort study involving 9073 patients treated in three fertility clinics in Brazil, Turkey and Vietnam between 2015 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women with infertility between 22 and 42 years old in their first IVF/ICSI cycle of standard ovarian stimulation whose fresh and/or frozen embryos were transferred until delivery of a live born or until all embryos were used. Patients were retrospectively classified according to the POSEIDON criteria into four groups based on female age, antral follicle count (AFC), and the number of oocytes retrieved or into a control group of normal responders (non-POSEIDON). POSEIDON patients encompassed younger (<35 years) and older (35 years or above) women with an AFC ≥5 and an unexpected poor (<4 retrieved oocytes) or suboptimal (4-9 retrieved oocytes) response to stimulation, and respective younger and older counterparts with an impaired ovarian reserve (i.e. expected poor responders; AFC <5). Non-POSEIDON patients were those with AFC ≥5 and >9 oocytes retrieved. CDR was computed per one aspirated cycle. Logistic regression analysis was carried out to examine the association between patient classification and CDR. MAIN RESULTS AND ROLE OF CHANCE: The CDR was lower in the POSEIDON patients than in the non-POSEIDON patients (33.7% vs 50.6%; P < 0.001) and differed across POSEIDON groups (younger unexpected poor responder [Group 1a; n = 212]: 27.8%, younger unexpected suboptimal responder [Group 1b; n = 1785]: 47.8%, older unexpected poor responder [Group 2a; n = 293]: 14.0%, older unexpected suboptimal responder [Group 2b; n = 1275]: 30.5%, younger expected poor responder [Group 3; n = 245]: 29.4%, and older expected poor responder [Group 4; n = 623]: 12.5%. Among unexpected suboptimal/poor responders (POSEIDON Groups 1 and 2), the CDR was twice as high in suboptimal responders (4-9 oocytes retrieved) as in poor responders (<4 oocytes) (P = 0.0004). Logistic regression analysis revealed that the POSEIDON grouping, number of embryos obtained, number of ET cycles per patient, number of oocytes collected, female age, duration of infertility and BMI were relevant predictors for CDR (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Our study relied on the antral follicle count as the biomarker used for patient classification. Ovarian stimulation protocols varied across study centers, potentially affecting patient classification. WIDER IMPLICATIONS OF THE FINDINGS: POSEIDON patients exhibit lower CDR per aspirated IVF/ICSI cycle than normal responders; the differences are mainly determined by female age and number of oocytes retrieved, thereby reflecting the importance of oocyte quality and quantity. Our data substantiate the validity of the POSEIDON criteria in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment. Efforts in terms of early diagnosis, prevention, and identification of specific interventions that might benefit POSEIDON patients are warranted. STUDY FUNDING/COMPETING INTEREST(S): Unrestricted investigator-sponsored study grant (MS200059_0013) from Merck KGaA, Darmstadt, Germany. The funder had no role in study design, data collection, analysis, decision to publish or manuscript preparation. S.C.E. declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. H.Y. declares receipt of payment for lectures from Merck and Ferring. L.N.V. receives speaker fees and conferences from Merck, Merck Sharp and Dohme (MSD) and Ferring and research grants from MSD and Ferring. J.F.C. declares receipt of statistical services fees from ANDROFERT Clinic. T.M.H. received speaker fees and conferences from Merck, MSD and Ferring. P.H. declares receipt of unrestricted research grants from Merck, Ferring, Gedeon Richter and IBSA and lecture fees from Merck, Gedeon Richter and Med.E.A. C.A. declares receipt of unrestricted research grants from Merck and lecture fees from Merck. The remaining authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Micronized progesterone plus dydrogesterone versus micronized progesterone alone for luteal phase support in frozen-thawed cycles (MIDRONE): a prospective cohort study.

STUDY QUESTION: Does the addition of oral dydrogesterone to vaginal progesterone as luteal phase support improve pregnancy outcomes during frozen embryo transfer (FET) cycles compared with vaginal progesterone alone? SUMMARY ANSWER: Luteal phase support with oral dydrogesterone added to vaginal progesterone had a higher live birth rate and lower miscarriage rate compared with vaginal progesterone alone. WHAT IS KNOWN ALREADY: Progesterone is an important hormone that triggers secretory transformation of the endometrium to allow implantation of the embryo. During IVF, exogenous progesterone is administered for luteal phase support. However, there is wide inter-individual variation in absorption of progesterone via the vaginal wall. Oral dydrogesterone is effective and well tolerated when used to provide luteal phase support after fresh embryo transfer. However, there are currently no data on the effectiveness of luteal phase support with the combination of dydrogesterone with vaginal micronized progesterone compared with vaginal micronized progesterone after FET. STUDY DESIGN, SIZE, DURATION: Prospective cohort study conducted at an academic infertility center in Vietnam from 26 June 2019 to 30 March 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1364 women undergoing IVF with FET. Luteal support was started when endometrial thickness reached ≥8 mm. The luteal support regimen was either vaginal micronized progesterone 400 mg twice daily plus oral dydrogesterone 10 mg twice daily (second part of the study) or vaginal micronized progesterone 400 mg twice daily (first 4 months of the study). In women with a positive pregnancy test, the appropriate luteal phase support regimen was continued until 7 weeks' gestation. The primary endpoint was live birth after the first FET of the started cycle, with miscarriage <12 weeks as one of the secondary endpoints. MAIN RESULTS AND THE ROLE OF CHANCE: The vaginal progesterone + dydrogesterone group and vaginal progesterone groups included 732 and 632 participants, respectively. Live birth rates were 46.3% versus 41.3%, respectively (rate ratio [RR] 1.12, 95% CI 0.99-1.27, P = 0.06; multivariate analysis RR 1.30 (95% CI 1.01-1.68), P = 0.042), with a statistically significant lower rate of miscarriage at <12 weeks in the progesterone + dydrogesterone versus progesterone group (3.4% versus 6.6%; RR 0.51, 95% CI 0.32-0.83; P = 0.009). Birth weight of both singletons (2971.0 ± 628.4 versus 3118.8 ± 559.2 g; P = 0.004) and twins (2175.5 ± 494.8 versus 2494.2 ± 584.7; P = 0.002) was significantly lower in the progesterone plus dydrogesterone versus progesterone group. LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were the open-label design and the non-randomized nature of the sequential administration of study treatments. However, our systematic comparison of the two strategies was able to be performed much more rapidly than a conventional randomized controlled trial. In addition, the single ethnicity population limits external generalizability. WIDER IMPLICATIONS OF THE FINDINGS: Our findings study suggest a role for oral dydrogesterone in addition to vaginal progesterone as luteal phase support in FET cycles to reduce the miscarriage rate and improve the live birth rate. Carefully planned prospective cohort studies with limited bias could be used as an alternative to randomized controlled clinical trials to inform clinical practice. STUDY FUNDING/COMPETING INTERESTS: This study received no external funding. LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; R.J.N. has received scientific board fees from Ferring and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant. TRIAL REGISTRATION NUMBER: NCT0399876.

Fresh embryo transfer versus freeze-only after in vitro maturation with a pre-maturation step in women with high antral follicle count: a randomized controlled pilot study.

PURPOSE: In vitro maturation (IVM) is an alternative to in vitro fertilization (IVF) for women at high risk of developing ovarian hyperstimulation syndrome (OHSS). This study determined the effectiveness and safety of a freeze-only strategy versus fresh embryo transfer (ET) after IVM with a pre-maturation step (CAPA-IVM) in women with a high antral follicle count (AFC). METHODS: This randomized, controlled pilot study (NCT04297553) was conducted between March and November 2020. Forty women aged 18-37 years with a high AFC (≥24 follicles in both ovaries) undergoing one cycle of CAPA-IVM were randomized to a freeze-only strategy with subsequent frozen ET (n = 20) or to fresh ET (n = 20). The primary endpoint was ongoing pregnancy resulting in live birth after the first ET of the started treatment cycle. RESULTS: The ongoing pregnancy rate in the freeze-only group (65%) was significantly higher than that in the fresh ET group (25%; p = 0.03), as was the live birth rate (60% versus 20%; p = 0.02). Clinical pregnancy rate was numerically, but not significantly, higher after frozen versus fresh ET (70% versus 35%; p = 0.06), while the number of day 3 or good quality embryos, endometrial thickness on the day of oocyte pick-up, implantation rate, and positive pregnancy test rate did not differ significantly between groups. No cases of OHSS were observed, and miscarriage and multiple pregnancy rates were similar in the two groups. CONCLUSIONS: These findings suggest that the effectiveness of CAPA-IVM could be improved considerably by using a freeze-only strategy followed by frozen ET in subsequent cycles. TRIAL REGISTRATION NUMBER: NCT04297553 ( www.clinicaltrials.gov ).

Epidemiology of viral disease outbreaks in Odisha, India (2010-2019).

Despite consistent public health efforts, the burden of viral disease in India remains high. The present study was undertaken to understand the aetiology, frequency and distribution of viral disease outbreaks in the state of Odisha between 2010 and 2019. This was a prospective study conducted at the Virology Research and Diagnostic Laboratory located at ICMR-Regional Medical Research Centre, Bhubaneswar, Odisha, wherein all the outbreaks of viral aetiologies were investigated and analysed to provide a comprehensive picture of the state of viral disease outbreaks in the region. A total of 191 suspected viral outbreaks were investigated by the team from VRDL during September 2010 and September 2019 reported from all the 30 districts of Odisha. Annual number of suspected cases ranged from 185 to 1002. The most commonly suspected outbreaks were of viral hepatitis (55 outbreaks; 1223 cases) followed by dengue (45 outbreaks; 1185 cases), chickenpox (30 outbreaks; 421 cases), viral encephalitis (27 outbreaks; 930 cases), measles (23 outbreaks; 464 cases), chikungunya (10 outbreaks; 593 cases) and rubella (1 outbreak; 60). The outbreaks peaked in frequency and intensity during the months of July and September. The epidemiology of viral disease outbreaks in the region is presented in the study. Health system preparedness based on evidence is essential for early detection and adequate response to such viral outbreaks.

The association between platelet dysfunction and adverse outcomes in cardiac surgical patients.

Haemostatic activation during cardiopulmonary bypass is associated with prothrombotic complications. Although it is not possible to detect and quantify haemostatic activation directly, platelet dysfunction, as measured with point-of-care-assays, may be a useful surrogate. In this study, we assessed the association between cardiopulmonary bypass-associated platelet dysfunction and adverse outcomes in 3010 cardiac surgical patients. Platelet dysfunction, as measured near the end of the rewarming phase of cardiopulmonary bypass, was calculated as the proportion of non-functional platelets after activation with collagen. Logistic regression and multivariable analyses were applied to assess the relationship between platelet dysfunction and a composite of in-hospital death; myocardial infarction; stroke; deep vein thrombosis or pulmonary embolism; and acute kidney injury (greater than a two-fold increase in creatinine). The outcome occurred in 251 (8%) of 3010 patients. The median (IQR [range]) percentage platelet dysfunction was less for those without the outcome as compared with those with the outcome; 14% (8-28% [1-99%]) vs. 19% (11-45% [2-98%]), p < 0.001. After risk adjustment, platelet dysfunction was independently associated with the composite outcome (p < 0.001), such that for each 1% increase in platelet dysfunction there was an approximately 1% increase in the composite outcome (OR 1.012; 95%CI 1.006-1.018). This exploratory study suggests that cardiopulmonary bypass-associated platelet dysfunction has prognostic value and may be a useful clinical measure of haemostatic activation in cardiac surgery.

Development and validation of the mastocytosis activity score.

BACKGROUND: Mastocytosis is a heterogeneous disease characterized by a clonal expansion of mast cells in various organs. The vast majority of patients suffer from signs and symptoms caused by mediator release from mast cells. Although the disease burden is high, there is currently no specific and validated instrument to measure and monitor signs and symptoms in patients with mastocytosis. OBJECTIVE: To develop and validate a disease-specific tool to measure and monitor the activity of signs and symptoms in patients with mastocytosis, the Mastocytosis Activity Score (MAS). METHODS: Nineteen potential MAS items were developed in a combined approach consisting of semi-structured patient interviews, expert input and literature research. Item selection was performed by impact analysis with 76 patients followed by a review for face validity. The resulting MAS was tested for validity, reliability and influence factors. In parallel, a US American English version of the MAS was developed. RESULTS: A total of 68 mastocytosis patients took part in the MAS validation study. The final 9-item MAS was found to have a three-domain structure ("skin," "gastrointestinal tract" and "other"), a valid total score and an excellent test-retest reliability. Multiple regression analysis revealed that disease duration, age or gender is not a significant determinant of the MAS results. CONCLUSIONS: The MAS is a disease-specific, valid and reliable patient-reported outcome measure for adult patients with cutaneous and indolent systemic mastocytosis. It may serve as a valuable tool to measure and monitor mastocytosis activity, both, in clinical trials and in routine care.

Effect of immunosuppressive therapies on survival of systemic lupus erythematosus: a propensity score analysis of a longitudinal cohort.

Objectives The aim of this study was to study the relationship between immunosuppressive drug treatment and survival in patients with systemic lupus erythematosus (SLE). Methods Patients who fulfilled four or more American College of Rheumatology criteria for SLE were followed longitudinally. Clinical characteristics, use of immunosuppressive agents and mortality were reviewed. Cox regression was used to study the relationship between immunosuppressive treatment and survival, adjusted for age, sex, vascular risk factors, organ damage, the anti-phospholipid antibodies and a propensity score for the indication of individual immunosuppressive agent derived from separate regression models. Results A total of 803 SLE patients were studied (92% women; age of SLE onset 33.2±14 years; follow-up time 10.8±7.7 years). The frequencies of ever use of immunosuppressive agents were: high-dose prednisolone (≥0.6 mg/kg/day for ≥4 weeks) (85%), azathioprine (63%), cyclophosphamide (25%), mycophenolate mofetil (27%), the calcineurin inhibitors (23%) and hydroxychloroquine (69%). Ninety-seven patients (12%) died and 56 (7%) patients were lost to follow-up. The causes of death were infection (44%), cerebrovascular events (12%), cardiovascular events (10%) and malignancy (8.2%). Cox regression revealed that the ever use of high-dose prednisolone, mycophenolate mofetil, calcineurin inhibitors or cyclophosphamide was not significantly associated with improved survival. However, the ever use of hydroxychloroquine (hazard ratio 0.59 (0.37-0.93); P=0.02) and azathioprine (hazard ratio 0.46 (0.28-0.75); P=0.002) was significantly associated with reduced mortality (41% and 54%, respectively) after adjustment for the propensity score and other confounding factors. A similar beneficial effect of hydroxychloroquine and azathioprine on survival was also observed in patients with lupus nephritis. Conclusions In this longitudinal cohort of Chinese SLE patients, the ever use of hydroxychloroquine and azathioprine was significantly associated with a probability of better survival. Treatment with high-dose prednisolone, cyclophosphamide, mycophenolate mofetil or the calcineurin inhibitors was not associated with long-term survival benefit.

Patient opinion of lower urinary tract symptoms and their treatment: a cross-sectional survey in Hong Kong public urology clinics.

INTRODUCTION: Lower urinary tract symptoms collectively represent a common condition among ageing men. There are, however, limited data on the frequency of individual symptoms in patients who seek specialist care. We conducted a multinational survey in South-East Asia to evaluate patients' self-reported prevalence, bother, treatment, and treatment satisfaction of four lower urinary tract symptoms namely, urgency, nocturia, slow stream, and post-micturition dribble. This report presents the analysis of the Hong Kong subpopulation. METHODS: This cross-sectional survey involved adult men aged over 18 years who attended a urology out-patient clinic because of lower urinary tract symptoms. A structured questionnaire, translated and validated in the local languages, was self-administered by patients. RESULTS: Of 1436 respondents surveyed in the region, 225 were from Hong Kong of whom most were aged 56 to 75 years, retired, and had no history of any previous prostate surgery. Overall, the self-reported prevalence of nocturia of at least one void per night was 93% (95% confidence interval, 90%-97%), slow stream 76% (71%-82%), post-micturition dribble 70% (64%-76%), and urgency 50% (43%-56%). Symptoms for which most respondents reported "some" or "a lot" of bother included: nocturia, defined as at least two voids per night (77%), and urgency and post-micturition dribble (73%). Only 39% to 54% of patients had previously received treatment but were not entirely satisfied with it. An understanding of their condition remained suboptimal. CONCLUSIONS: In Hong Kong, nocturia emerged as the most prevalent and one of the most bothersome symptoms among men who sought urologist care for lower urinary tract symptoms. Compared with the non-Hong Kong population, Hong Kong respondents tended to be highly symptomatic and bothered. They were, however, less likely to have received treatment and were generally less satisfied with previous treatment.

Real-time estimation of the hospitalization fatality risk of influenza A(H1N1)pdm09 in Hong Kong.

During the early stage of an epidemic, timely and reliable estimation of the severity of infections are important for predicting the impact that the influenza viruses will have in the population. We obtained age-specific deaths and hospitalizations for patients with laboratory-confirmed H1N1pdm09 infections from June 2009 to December 2009 in Hong Kong. We retrospectively obtained the real-time estimates of the hospitalization fatality risk (HFR), using crude estimation or allowing for right-censoring for final status in some patients. Models accounting for right-censoring performed better than models without adjustments. The risk of deaths in hospitalized patients with confirmed H1N1pdm09 increased with age. Reliable estimates of the HFR could be obtained before the peak of the first wave of H1N1pdm09 in young and middle-aged adults but after the peak in the elderly. In the next influenza pandemic, timely estimation of the HFR will contribute to risk assessment and disease control.

MATTHEW-WOOD SYNDROME: A CASE WITH DEXTROCARDIA AND STREAK GONADS.

Matthew-Wood syndrome (MWS), also termed Microphthalmia, syndrome 9 (MCOPS9, MIM 601186), Spear syndrome, or pulmonary hypoplasia, diaphragmatic hernia, anophthalmia and cardiac defects syndrome (PDAC syndrome), is an autosomal recessive disorder characterised by ocular, respiratory and cardiac abnormalities. Mutations in retinoic acid 6 gene (STRA6) have been reported in clinically diagnosed patients with MWS. Here we presented a case with MWS, who has characteristic findings of the syndrome as well as dextrocardia as an undescribed feature, and bilateral streak gonads which was described only in one patient previously. Molecular analysis showed a homozygous exonic missense mutation in the STRA6 gene.

Participant evaluation of simulation training using crew resource management in a hospital setting in Hong Kong.

INTRODUCTION: A simulation team-based crew resource management training programme was developed to provide a unique multidisciplinary learning experience for health care professionals in a regional hospital in Hong Kong. In this study, we evaluated how health care professionals perceive the programme. METHODS: A cross-sectional questionnaire survey was conducted in the Multidisciplinary Simulation and Skills Centre at Queen Elizabeth Hospital in Hong Kong. A total of 55 individuals in the departments of Obstetrics and Gynaecology, Anaesthesiology and Operating Theatre Services, Intensive Care Unit, and Accident and Emergency participated in the study between June 2013 and December 2013. The course content was specially designed according to the needs of the clinical departments and comprised a lecture followed by scenarios and debriefing sessions. Principles of crew resource management were introduced and taught throughout the course by trained instructors. Upon completion of each course, the participants were surveyed using a 5-point Likert scale and open-ended questions. RESULTS: The participant's responses to the survey were related to course organisation and satisfaction, realism, debriefing, and relevance to practice. The overall rating of the training programme was high, with mean Likert scale scores of 4.1 to 4.3. The key learning points were identified as closed-loop communication skills, assertiveness, decision making, and situational awareness. CONCLUSIONS: The use of a crew resource management simulation-based training programme is a valuable teaching tool for frontline health care staff. Concepts of crew resource management were relevant to clinical practice. It is a highly rated training programme and our results support its broader application in Hong Kong.

Effect of golimumab and pamidronate on clinical efficacy and MRI inflammation in axial spondyloarthritis: a 48-week open randomized trial.

OBJECTIVES: To compare the effect of golimumab (GLM) and pamidronate (PAM) on clinical efficacy and magnetic resonance imaging (MRI) inflammation in axial spondyloarthritis (aSpA). METHOD: Patients who fulfilled the Assessment of SpondyloArthritis Society (ASAS) criteria for aSpA and had active disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4] were randomized in a 2:1 ratio to receive either GLM (50 mg) or PAM (60 mg) 4 weekly for 48 weeks. Clinical efficacy was assessed at intervals. Inflammation of the spine and sacroiliac joints (SIJs) on MRI was graded by the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. RESULTS: Twenty patients were assigned to GLM and 10 to PAM (83% men; age 33.4 ± 10.9 years; disease duration 4.4 ± 3.4 years). The baseline characteristics of the two groups were similar. At week 48, the proportions of patients who achieved an ASAS20 response were not significantly different between the GLM and PAM groups (65% vs. 56%; p = 0.69). Although there were no differences in BASDAI, spinal pain, and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) scores between the two groups at week 48, the Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were significantly lower in GLM-treated patients. The SPARCC scores of the spine and SIJs decreased significantly in GLM- but not in PAM-treated patients. The differences in SPARCC scores between the two groups at week 48 were statistically significant. The frequency of adverse events (AEs) was similar in both arms. CONCLUSIONS: In patients with aSpA, the clinical response rate and improvement in pain and quality of life (QoL) were similar between GLM and PAM groups after 48 weeks. However, significant reduction in inflammatory markers and MRI inflammation was only observed with GLM treatment.

Long-term outcome of rheumatoid arthritis defined according to the 2010-classification criteria.

OBJECTIVE: The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for rheumatoid arthritis (RA) have been thoroughly studied for the test characteristics but it is unclear whether '2010 RA' has a different phenotype than '1987 RA' when assessing the severity of the disease course. Therefore this study compared two long-term disease outcomes. METHODS: 1502 early arthritis patients that had no other diagnoses than RA or undifferentiated arthritis (UA) were studied on fulfilling the 1987 ACR criteria, 2010 criteria or both. The severity of joint damage was studied with yearly radiographs over 7 years. Achieving disease-modifying anti-rheumatic drug (DMARD)-free sustained remission was assessed over 10-years follow-up. Multivariate normal regression and Cox-proportional hazard regression were used, adjusting for age, gender and treatment. RESULTS: 550 patients fulfilled the 1987 criteria, 788 patients the 2010 criteria and 489 both criteria sets. Patients fulfilling the 2010 criteria developed less severe radiological joint damage (p=0.023) and achieved DMARD-free sustained remission more often (HR=1.18 (0.93-1.50)) than patients fulfilling the 1987 criteria, though the latter was not statistically significant. All 1987+2010- patients were anti-citrullinated peptide antibody (ACPA)-negative. When also applying the radiologic criterion of the 2010-criteria, half of the 1987+2010- patients became 2010 criteria positive, but results on the long-term outcome remained similar. CONCLUSIONS: '2010 RA' has a milder disease course than '1987 RA'. This may have important implications for basic scientific studies and clinical trials in RA.

The effects of hyperuricaemia on flow-mediated and nitroglycerin-mediated dilatation in high-risk patients.

BACKGROUND AND AIMS: Uric acid is emerging as one of the newer risk markers to consider in the cardiovascular risk assessment because it is demonstrated to be associated with adverse cardiovascular outcomes, particularly in high cardiovascular risk patients. One of the proposed mechanisms involving hyperuricaemia is the development of vascular damage. The aim of this study is to examine the role of hyperuricaemia on vascular function in patients with high cardiovascular risk. METHODS AND RESULTS: We examined the clinical significance of hyperuricaemia in relation to vasomotor response of the brachial artery by using high-resolution ultrasound in 304 subjects with coronary artery disease and/or diabetes. Nitroglycerin-mediated dilatation (NMD) was significantly lower in the hyperuricaemic group compared with the normouricaemic group (12.8 ± 6.9% vs. 16.2 ± 7.7%, p < 0.001), but no significant difference was observed in flow-mediated dilatation (FMD) between the two groups [3.78 (95% CR: 1.5-9.9) vs. 3.88 (95% CR: -2.6 to 9.9), p = 0.78]. Multivariate analysis demonstrated that smoking was the strongest predictor of FMD (b = -0.81, p = 0.02); and that smoking (b = -2.62, p = 0.003), SBP (b = -0.11, p = 0.001), hyperuricaemia (b = -2.11, p = 0.02) and use of nitrates (b = -3.30, p = 0.001) were independent predictors of NMD. CONCLUSION: High cardiovascular risk patients with hyperuricaemia had a lower NMD than those with normouricaemia. Importantly, hyperuricaemia was independently associated with NMD after multivariable adjustments. To further understand the pathophysiological mechanisms involving hyperuricaemia, particularly in the context of impaired NMD, further experimental and clinical studies are needed.

Evaluating the protective efficacy of antigen combinations against Photobacterium damselae ssp. piscicida infections in cobia, Rachycentron canadum L.

Cobia, Rachycentron canadum L., is a very important aquatic fish that faces the risk of infection with the bacterial pathogen Photobacterium damselae ssp. piscicida, and there are few protective approaches available that use multiple antigens. In the present study, potent bivalent antigens from P. damselae ssp. piscicida showed more efficient protection than did single antigens used in isolation. In preparations of three antigens that included recombinant heat shock protein 60 (rHSP60), recombinant α-enolase (rENOLASE) and recombinant glyceraldehyde-3-phosphate dehydrogenase (rGAPDH), we analysed the doses that elicited the best immune responses and found that this occurred at a total of 30 µg of antigen per fish. Subsequently, vaccination of fish with rHSP60, rENOLASE and rGAPDH achieved 46.9, 52 and 25% relative per cent survival (RPS), respectively. In addition, bivalent subunit vaccines--combination I (rHSP60 + rENOLASE), combination II (rENOLASE + rGAPDH) and combination III (rHSP60 + rGAPDH)--were administered and the RPS in these groups (65.6, 64.0 and 48.4%, respectively), was higher than that achieved with single-antigen administration. Finally, in combination IV, the trivalent vaccine rHSP60 + rENOLASE + rGAPDH, the RPS was 1.6%. Taken together, our results suggest that combinations of two antigens may achieve a better efficiency than monovalent or trivalent antigens, and this may provide new insights into pathogen prevention strategies.