Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial

Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment

The epidemiology and natural history of depressive disorders in Hong Kong's primary care

Background: Depressive disorders are commonly managed in primary care and family physicians are ideally placed to serve as central providers to these patients. Around the world, the prevalence of depressive disorders in patients presenting to primary care is between 10-20%, of which around 50% remain undiagnosed. In Hong Kong, many barriers exist preventing the optimal treatment and management of patients with depressive disorders. The pathways of care, the long term outcomes and the factors affecting prognosis of these patients requires closer examination. Methods/Design. The aim of this study is to examine the prevalence, incidence and natural history of depressive disorders in primary care and the factors influencing diagnosis, management and outcomes using a cross-sectional study followed by a longitudinal cohort study. Doctors working in primary care settings across Hong Kong have been invited to participate in this study. On one day each month over twelve months, patients in the doctor's waiting room are invited to complete a questionnaire containing items on socio-demography, co-morbidity, family history, previous doctor-diagnosed mental illness, recent mental and other health care utilization, symptoms of depression and health-related quality of life. Following the consultation, the doctors provide information regarding presenting problem, whether they think the patient has depression, and if so, whether the diagnosis is new or old, and the duration of the depressive illness if not a new diagnosis. If the doctor detects a depressive disorder, they are asked to provide information regarding patient management. Patients who consent are followed up by telephone at 2, 12, 26 and 52 weeks. Discussion. The study will provide information regarding cross-sectional prevalence, 12 month incidence, remission rate, outcomes and factors affecting outcomes of patients with depressive disorders in primary care. The epidemiology, outcomes, pathways of care, predictors for prognosis and service needs for primary care patients with depressive disorders will be described and recommendations made for policy and service planning. © 2011 Chin et al; licensee BioMed Central Ltd.published_or_final_versio

Developing a core outcome set for future infertility research : An international consensus development study

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Trends in the incidence of acute watery diarrhoea in the Lao People's Democratic Republic, 2009-2013

Diarrhoeal disease is the second leading cause of death in children under age 5 worldwide, with rotavirus being the main etiology. In the Lao People's Democratic Republic, acute watery diarrhoea (AWD) was introduced as one of the national notifiable diseases in 2004. We retrospectively reviewed the aggregate (n = 117 277) and case-based (n = 67 755) AWD surveillance data from 2009 to 2013 reported weekly from 1115 health facilities nationwide. Rotavirus rapid test data from all eight sentinel sites in Vientiane Capital in 2013 were also collected for analysis. The incidence of AWD ranged between 215 and 476 cases per 100 000 population and increased from 2009 to 2012 when it levelled off. The most affected age group was children under 5 who were about seven to nine times more likely to have AWD than the rest of the population (P < 0.0001). In children under 5, 74.8% of the cases were aged 0-24 months and AWD was 1.28 times more common in males (P < 0.0001). Among the 230 stool specimens tested in children under 5 in 2013, 109 (47.4%) tested positive for rotavirus. The increased AWD incidence over the study period may reflect a true increase in AWD or an improved sensitivity of the system. We recommend new mothers breastfeed up to two years after birth, which is known to reduce AWD morbidity and mortality in young children. We also recommend conducting rotavirus disease burden and cost-effectiveness studies to explore the benefits of introduction of rotavirus vaccine

Trends in the incidence of acute watery diarrhoea in the Lao People's Democratic Republic, 2009-2013

Diarrhoeal disease is the second leading cause of death in children under age 5 worldwide, with rotavirus being the main etiology. In the Lao People's Democratic Republic, acute watery diarrhoea (AWD) was introduced as one of the national notifiable diseases in 2004. We retrospectively reviewed the aggregate (n = 117 277) and case-based (n = 67 755) AWD surveillance data from 2009 to 2013 reported weekly from 1115 health facilities nationwide. Rotavirus rapid test data from all eight sentinel sites in Vientiane Capital in 2013 were also collected for analysis. The incidence of AWD ranged between 215 and 476 cases per 100 000 population and increased from 2009 to 2012 when it levelled off. The most affected age group was children under 5 who were about seven to nine times more likely to have AWD than the rest of the population (P < 0.0001). In children under 5, 74.8% of the cases were aged 0-24 months and AWD was 1.28 times more common in males (P < 0.0001). Among the 230 stool specimens tested in children under 5 in 2013, 109 (47.4%) tested positive for rotavirus. The increased AWD incidence over the study period may reflect a true increase in AWD or an improved sensitivity of the system. We recommend new mothers breastfeed up to two years after birth, which is known to reduce AWD morbidity and mortality in young children. We also recommend conducting rotavirus disease burden and cost-effectiveness studies to explore the benefits of introduction of rotavirus vaccine

Hidden varicella outbreak, Luang Prabang Province, Lao People's Democratic, December 2014 to January 2015

Background: In January 2015, the Lao People’s Democratic Republic Ministry of Health received a report of 34 cases of fever and rash with one laboratory-confirmed measles case in Houitone village, Pakseng District of Luang Prabang Province. Between 21 and 27 January, we conducted a field investigation to determine the etiology, magnitude and severity of this outbreak. Methods: We conducted active case findings in Houitone and neighbouring villages and collected information on age, location, date of rash onset, symptoms and measles vaccination status. We collected serum samples from cases with rash onset of less than 28 days and tested for measles and rubella IgM using enzyme-linked immunosorbent assay. Results: Between 22 December 2014 and 23 January 2015, 190 fever and rash cases were identified in seven villages in Pakseng District with the majority of the cases in Houitone village. The most affected age group was between 1 and 9 years. The majority of the rashes were vesicular. Of the additional 43 serum samples collected, no samples tested positive for measles or rubella IgM. The clinical manifestation and epidemiology of the disease suggested a varicella outbreak. Conclusion: The rapid response to a single laboratory-confirmed measles case did not identify a measles outbreak but suggested a varicella outbreak. Low measles vaccination coverage led us to recommend a routine catch-up vaccination campaign. We also recommend collecting information of rash types and photos of rashes in future fever and rash outbreaks to better differentiate potential etiologies

CK2 Inhibits TIMELESS Nuclear Export and Modulates CLOCK Transcriptional Activity to Regulate Circadian Rhythms.

Circadian clocks orchestrate daily rhythms in organismal physiology and behavior to promote optimal performance and fitness. In Drosophila, key pacemaker proteins PERIOD (PER) and TIMELESS (TIM) are progressively phosphorylated to perform phase-specific functions. Whereas PER phosphorylation has been extensively studied, systematic analysis of site-specific TIM phosphorylation is lacking. Here, we identified phosphorylation sites of PER-bound TIM by mass spectrometry, given the importance of TIM as a modulator of PER function in the pacemaker. Among the 12 TIM phosphorylation sites we identified, at least two of them are critical for circadian timekeeping as mutants expressing non-phosphorylatable mutations exhibit altered behavioral rhythms. In particular, we observed that CK2-dependent phosphorylation of TIM(S1404) promotes nuclear accumulation of PER-TIM heterodimers by inhibiting the interaction of TIM and nuclear export component, Exportin 1 (XPO1). We propose that proper level of nuclear PER-TIM accumulation is necessary to facilitate kinase recruitment for the regulation of daily phosphorylation rhythm and phase-specific transcriptional activity of CLOCK (CLK). Our results highlight the contribution of phosphorylation-dependent nuclear export of PER-TIM heterodimers to the maintenance of circadian periodicity and identify a new mechanism by which the negative elements of the circadian clock (PER-TIM) regulate the positive elements (CLK-CYC). Finally, because the molecular phenotype of tim(S1404A) non-phosphorylatable mutant exhibits remarkable similarity to that of a mutation in human timeless that underlies familial advanced sleep phase syndrome (FASPS), our results revealed an unexpected parallel between the functions of Drosophila and human TIM and may provide new insights into the molecular mechanisms underlying human FASPS