GDF15 linked to maternal risk of nausea and vomiting during pregnancy.

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1-4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with ß-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

Adapting a Clinical Practice Guideline for Management of Patients with Knee and Hip Osteoarthritis by Hong Kong Physiotherapists.

Knee and hip osteoarthritis are common disabling conditions globally. Although numerous international clinical practice guidelines exist to guide physiotherapy management, not all recommendations issued from these guidelines can be translated to other contexts without considering the cultural acceptability and clinical implementability of targeted countries. Because the ADAPTE framework provides a robust methodology to adapt guidelines to the local context, this study used its methodology to adapt high-quality guideline recommendations to promote optimal physiotherapy care for knee and hip osteoarthritis in Hong Kong. The ADAPTE framework was used and modified to complete the adaptation process. International clinical practice guidelines were identified from eight guideline clearinghouses and six electronic databases. Two independent reviewers critically appraised the eligible guidelines using the AGREE II tool. We extracted and tabulated recommendations from high-quality guidelines. A voting-based consensus among interdisciplinary experts was conducted to decide on suitable recommendations for the Hong Kong context and whether there was a need to modify them. Pertinent recommendations were then translated into the traditional Chinese language. Our team members suggested modifying four tools and adding one to explore the patient's feedback on the recommendations, to the ADAPTE framework. The adaptation was performed on three high-quality guidelines. We adapted 28 and 20 recommendations for treating knee and hip osteoarthritis, respectively. We recommend a multimodal treatment for managing knee and hip osteoarthritis. Land- and aquatic-based exercises, patient education, and self-management were strongly recommended for patients with knee osteoarthritis. Land- and aquatic-based exercises were strongly recommended for patients with hip osteoarthritis. This is the first adaptation study in Hong Kong. It provides guidance to local physiotherapists on managing patients with knee and hip osteoarthritis. Future studies should test the effectiveness of implementing this adapted guideline to improve local physiotherapy care in Hong Kong.

Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy.

Human pregnancy is frequently accompanied by nausea and vomiting that may become severe and life-threatening, as in hyperemesis gravidarum (HG), the cause of which is unknown. Growth Differentiation Factor-15 (GDF15), a hormone known to act on the hindbrain to cause emesis, is highly expressed in the placenta and its levels in maternal blood rise rapidly in pregnancy. Variants in the maternal GDF15 gene are associated with HG. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We found that the great majority of GDF15 in maternal circulation is derived from the feto-placental unit and that higher GDF15 levels in maternal blood are associated with vomiting and are further elevated in patients with HG. Conversely, we found that lower levels of GDF15 in the non-pregnant state predispose women to HG. A rare C211G variant in GDF15 which strongly predisposes mothers to HG, particularly when the fetus is wild-type, was found to markedly impair cellular secretion of GDF15 and associate with low circulating levels of GDF15 in the non-pregnant state. Consistent with this, two common GDF15 haplotypes which predispose to HG were associated with lower circulating levels outside pregnancy. The administration of a long-acting form of GDF15 to wild-type mice markedly reduced subsequent responses to an acute dose, establishing that desensitisation is a feature of this system. GDF15 levels are known to be highly and chronically elevated in patients with beta thalassemia. In women with this disorder, reports of symptoms of nausea or vomiting in pregnancy were strikingly diminished. Our findings support a causal role for fetal derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to GDF15, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

MC3R links nutritional state to childhood growth and the timing of puberty.

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.

Development of a short form of the Hong Kong Chinese orebro musculoskeletal pain screening questionnaire.

BACKGROUND: The Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ) is a valid screening tool to identify those musculoskeletal patients at risk of developing chronicity and disability. A Hong Kong Chinese version of the OMPSQ (COMPSQ-HK) was developed with satisfactory construct validity and predictive validity. OBJECTIVE: The aim of this study was to develop a 10-item short form of the COMPSQ-HK (COMPSQ-HK10) and examine its measurement properties. METHODS: The 10 items were identified from the suggestion by the original author of OMPSQ. The data of the 10 items were extracted from the main study to develop the COMPSQ-HK conducted from 2010 to 2013. The internal consistency using Cronbach's alpha, test-retest reliability examining intraclass correlation coefficient (ICC 1 , 1 ), minimum detectable change and 95% limits of agreement, construct validity by correlating COMPSQ-HK10 with pain, disability score, kinesiophobia score and Medical Outcomes Study Short Form 12, and predictive validity investigating receiver operating characteristic (ROC) curve analyses with sick leave > 60 days and return-to-work status at one year were calculated. RESULTS: A total of 305 back patients and 160 neck patients were recruited with about 30% of patients lost to follow-up at one year. Both the internal consistency (Cronbach's alpha as 0.732 to 0.757) and test-retest reliabilities (ICC 1 , 1 as 0.868 for both back and neck patients) were satisfactory. The correlations between COMPSQ-HK10 and COMPSQ-HK for back and neck patients were excellent (Pearson r as 0.919 and 0.896, respectively, p < 0 . 001 ). The areas under the ROC curves for back and neck patients were similar for COMPSQ-HK10 and COMPSQ-HK, ranging from 0.603 to 0.712. A cut-off score of 54 of COMPSQ-HK10 was recommended in predicting "sick leave of more than 60 days at one year" and "return to work for at least four consecutive weeks at one year". CONCLUSION: The COMPSQ-HK10 has comparable measurement properties with the COMPSQ-HK. It is recommended to use the COMPSQ-HK10 for routine screening to identify patients of back and neck pain at risk of developing chronic pain and disability.

Pain management programme for Chinese patients: a 10-year outcome review.

OBJECTIVES: To review the clinical and social benefits of a pain management programme in Hong Kong. DESIGN: Prospective cohort study. SETTING: Tertiary out-patient clinic, Hong Kong. PARTICIPANTS: Patients with chronic non-cancer pain and prolonged (mean, 46 months) psychosocial disability who joined the Comprehensive Outpatient Pain Engagement programme between 2002 and 2012. INTERVENTION: A structured 6-week out-patient pain rehabilitation course designed to improve function and reduce disability, regardless of the cause or severity of pain. MAIN OUTCOME MEASURES: Social outcomes included return-to-work rate, hospital admissions, and out-patient visits. Physical outcomes included tolerance to sitting and standing. Psychological constructs such as mood, catastrophisation, self-efficacy, quality of life, and perceived performances were used. Each measure was taken before and 1 year after the programme. RESULTS: There was significant increase in return-to-work rate 1 year after commencement of the programme (35% after vs 17% before the programme; odds ratio=3.01), reduction in medical utilisation, and improvement in all physical and psychological measures. Pain intensity, psychological distress, and history of work-related injuries were not related to the likelihood of return to work. Shorter duration of pain and higher physical functioning score in 36-Item Short-Form Health Survey were prognostic indicators. CONCLUSIONS: Patients with chronic pain who joined the Comprehensive Outpatient Pain Engagement programme showed significant functional improvement despite the long history of pain.

The application of participatory ergonomics in a healthcare setting in Hong Kong.

BACKGROUND: Work-related musculoskeletal disorders (WRMDs) are recognized as a major source of significant pain and disability in the healthcare sector. However, they are preventable if appropriate surveillance and intervention programs are implemented. OBJECTIVE: The purpose of this paper is to describe the holistic ergonomic approach that was used to address the multifactorial problems encountered by healthcare workers in their daily work. METHODS: Using participatory ergonomics, healthcare workers in this study teamed up with management and staff with expertise in ergonomic analysis, design, and implementation of remedies. Selected participatory ergonomic intervention programs targeted at an organizational level are elaborated. Interventions included pre-work stretching, workplace surveillance at a psychiatric department, on-site ergonomic teaching for community nurses, and display screen equipment consultancy. DISCUSSIONS: Changes in workplace design, equipment re-arrangement, awareness of proper posture, and adoption of good work practices all play important roles in reducing musculoskeletal disorders among healthcare workers. Prompt occupational medicine and rehabilitation services were also provided to complement the work disability prevention process. The impact of the various intervention programs on staff health, costs and productivity of the organization are simultaneously discussed.

The predictive validity of OMPQ on the rehabilitation outcomes for patients with acute and subacute non-specific LBP in a Chinese population.

INTRODUCTION: Early screening of physical and psychosocial risk factors has been advocated as a way to identify low back pain (LBP) patients who may develop chronic disability. This study evaluated the predictive validity of a Chinese version of the Orebro Musculoskeletal Pain Questionnaire (OMPQ) in identifying LBP patients at risk of developing poor return-to-work (RTW) outcomes. METHODS: Altogether 241 patients with acute or subacute non-specific LBP agreed to participate, and they were screened at baseline with OMPQ, and evaluated after discharge from physiotherapy (n = 173) with outcome measures including the Roland-Morris Disability Questionnaire (RMDQ), numerical pain score (0-10) and global recovery (0-10). At 1-year follow-up, information on RTW status as well as sick leave duration were obtained. RESULTS: At baseline the OMPQ had a mean score of 112.0 (SD = 26.5). The receiver operator characteristic (ROC) curves of OMPQ scores at 1-year follow-up recorded values of area under the curve of 0.693 for RTW and 0.714 for sick leave duration, which are comparable to those reported in European studies. OMPQ was the only factor that could significantly predict the RTW outcomes, compared to other variables such as the RMDQ scores. CONCLUSION: The results confirmed the predictive validity of the Chinese version of OMPQ in screening LBP patients at risk of developing poor occupational outcomes, and appropriate interventions can be arranged for these high-risk individuals in the rehabilitation process.

Clinical spectrum of human rhinovirus infections in hospitalized Hong Kong children.

BACKGROUND: Human rhinovirus (HRV) is classified into A, B, and C genogroups. HRVs cause mild upper respiratory infections, but HRV-C was recently found to be a major cause of asthma exacerbation in whites. This study elucidated disease spectrum of HRV infections among Hong Kong children hospitalized with respiratory illnesses. METHODS: This retrospective study recruited 128 children with asthma exacerbations and 192 inpatient controls without allergy and hospitalized for respiratory illnesses within the same week. Their clinical information was retrieved from case records. HRVs in nasopharyngeal aspirates were detected by molecular assays using primers targeting consensus VP4/VP2 coding regions, and their genogroups identified by sequencing. RESULTS: The mean (standard deviation) age of cases and controls was 5.6 (3.6) years and 5.4 (3.8) years, respectively (P = 0.601). HRV was detected in 107 (84.9%) cases and 63 (33.0%) controls (P < 0.0001), and HRV-C in 69.8% and 18.8% of these groups, respectively (P < 0.0001). Detection of HRV-A and -B was similar between these groups (P > 0.15). More subjects with HRV-C needed oxygen supplementation (11.1% vs. 2.6%; P = 0.043). Among controls, HRV infection was associated with acute bronchiolitis (P < 0.001) and bronchitis (P = 0.04), which paralleled those of HRV-C. HRV-A was associated with acute bronchiolitis (P = 0.005). Phylogenetic analysis revealed a diverse group of HRV serotypes (21 for HRV-A, 2 for HRV-B, and 32 for HRV-C). CONCLUSIONS: HRV-C is associated with asthma exacerbation, whereas the presence of all HRVs, or either HRV-A or HRV-C alone, is associated with wheezing respiratory infections in nonasthmatic children. HRV is an important respiratory virus responsible for childhood wheezing illnesses.

The functional capacity of healthcare workers with history of severe acute respiratory distress syndrome (SARS) complicated with avascular necrosis--case report.

Two years after the SARS outbreak in Hong Kong, 128 healthcare workers continued to present with musculoskeletal complaints and 38 workers were diagnosed with avascular necrosis (AVN) in different joints. 13 healthcare workers were referred to six designated Physiotherapy Departments of the Hospital Authority for a tailor-made standardized Functional Capacity Evaluation (FCE) from 2004 to 2005 on a voluntary basis. Job analysis, workers' self-perceived disability and functional capacity, non-material handling tests, and the cardiopulmonary fitness test were performed. Retrospective review of the FCE data showed that there were 17 AVN of hips, 16 AVN of knees, 3 AVN of shoulders. All patients had AVN of lower limb joints. Nearly full ranges of movement (ROM) were observed in the knees involved, but the hip range was decreased for most subjects suffering from hip AVNs. Most workers (n=12) could not complete the cardiopulmonary test due to intolerable joint pain. Six workers' self-perceived physical demands level (PDC) matched with the physical demands level identified by the FCE. 12 healthcare workers attained a sedentary physical demands level and were unable to match with their previous job demands. One staff was classified as light physical demands and managed his original duty. Four workers had returned to work at the time FCE was performed. The tailor-made FCE added information to facilitate the return-to-work planning for the staff. Four more workers returned to work with modified duties one year after the FCE.