Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.

The diagnosis of functional constipation (FC) relies on patient-reported outcomes evaluated as criteria based on the clustering of symptoms. Although the ROME IV criteria for FC diagnosis is relevant for a multicultural population(1), how an individual’s lifestyle, environment and culture may influence the pathophysiology of FC remains a gap in our knowledge. Building on insights into mechanisms underpinning disorders of gut-brain interactions (formerly functional gastrointestinal disorders) in the COMFORT Cohort(2), this study aimed to investigate the differences in gastrointestinal (GI) symptom scores among participants with FC in comparison to healthy controls between Chinese and non-Chinese New Zealanders. The Gastrointestinal Understanding of Functional Constipation In an Urban Chinese and Urban non-Chinese New Zealander Cohort (GUTFIT) study was a longitudinal cohort study, which aimed to determine a comprehensive profile of characteristics and biological markers of FC between Chinese and non-Chinese New Zealanders. Chinese (classified according to maternal and paternal ethnicity) or non-Chinese (mixed ethnicities) adults living in Auckland classified as with or without FC based on ROME IV were enrolled. Monthly assessment (for 3 months) of GI symptoms, anthropometry, quality of life, diet, and biological samples were assessed monthly over March to June 2023. Demographics were obtained through a self-reported questionnaires and GI symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) and Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS). This analysis is a cross-sectional assessment of patient-reported outcomes of GI symptoms. Of 78 enrolled participants, 66 completed the study (male, n = 10; female, n = 56) and were distributed across: Chinese with FC (Ch-FC; n = 11), Chinese control (Ch-CON; n = 19), non-Chinese with FC (NCh-FC; n = 16), non-Chinese control (NCh-CON; n = 20). Mean (SD) age, body mass index, and waist circumference were 40 ± 9 years, 22.7 ± 2.5 kg/m2, and 78.0 ± 7.6 cm, respectively. Ethnicity did not impact SAGIS domain scores for GI symptoms (Ethnicity x FC severity interaction p>0.05). Yet, the constipation symptoms domain of the GSRS was scored differently depending on ethnicity and FC status (Ethnicity x FC interaction p<0.05). In post hoc comparison, NCh-FC tended to have higher GSRS constipation severity scores than Ch-FC (3.4 ± 1.0 versus 3.8 ± 0.8 /8, p<0.1) Although constipation symptom severity tended to be higher in NCh-FC, on the whole, ethnicity did not explain variation in this cohort. FC status was a more important predictor of GI symptoms scores. Future research will assess differences in symptom burden to explore ethnicity-specific characteristics of FC.

Distinct pathophysiology has been identified with disorders of gut-brain interactions (DGBI), including functional constipation (FC)(1,2), yet the causes remain unclear. Identifying how modifiable factors (i.e., diet) differ depending on gastrointestinal health status is important to understand relationships between dietary intake, pathophysiology, and disease burden of FC. Given that dietary choices are culturally influenced, understanding ethnicity-specific diets of individuals with FC is key to informing appropriate symptom management and prevention strategies. Despite distinct genetic and cultural features of Chinese populations with increasing FC incidence(3), DGBI characteristics are primarily described in Caucasian populations(2). We therefore aimed to identify how dietary intake of Chinese individuals with FC differs to non-Chinese individuals with FC, relative to healthy controls. The Gastrointestinal Understanding of Functional Constipation In an Urban Chinese and Urban non-Chinese New Zealander Cohort (GUTFIT) study was a longitudinal case-control study using systems biology to investigate the multi-factorial aetiology of FC. Here we conducted a cross-sectional dietary intake assessment, comparing Chinese individuals with FC (Ch-FC) against three control groups: a) non-Chinese with FC (NCh-FC) b) Chinese without FC (Ch-CON) and c) non-Chinese without FC (NCh-CON). Recruitment from Auckland, New Zealand (NZ) identified Chinese individuals based on self-identification alongside both parents self-identifying as Chinese, and FC using the ROME IV criteria. Dietary intake was captured using 3-day food diaries recorded on consecutive days, including one weekend day. Nutrient analysis was performed by Foodworks 10 and statistical analysis with SPSS using a generalised linear model (ethnicity and FC status as fixed factors). Of 78 enrolled participants, 66 completed the study and 64 (39.4 ± 9.2 years) completed a 3-day food diary at the baseline assessment. More participants were female (84%) than male (16%). FC and ethnicity status allocated participants into 1 of 4 groups: Ch-FC (n = 11), Ch-CON (n = 18), NCh-FC (n = 16), NCh-CON (n = 19). Within NCh, ethnicities included NZ European (30%), non-Chinese Asian (11%), Other European (11%), and Latin American (2%). Fibre intake did not differ between Ch-FC and NCh-FC (ethnicity × FC status interaction p>0.05) but was independently lower overall for FC than CON individuals (21.8 ± 8.7 versus 27.0 ± 9.7 g, p<0.05) and overall for Ch than NCh (22.1 ± 8.0 versus 27.0 ± 10.4 g, p<0.05). Carbohydrate, protein, and fat intakes were not different across groups (p>0.05 each, respectively). In the context of fibre and macronutrient intake, there is no difference between Ch-FC and NCh-FC. Therefore, fibre and macronutrients are unlikely to contribute to potential pathophysiological differences in FC between ethnic groups. A more detailed assessment of dietary intake concerning micronutrients, types of fibre, or food choices may be indicated to ascertain whether other dietary differences exist.

Twenty-four primiparous pregnant pigs were randomly assigned to three handling treatments: Minimal, Positive and Negative. The pigs were moved individually to indoor concrete-floored partial stalls with neck-tethers, 2 days before handling commenced. Positive (stroking and patting on approach to an experimenter) and Negative (brief electric shock of < Is when failing to withdraw from the outstretched hand of an experimenter) handling was imposed for 3min day-1 and the amount of physical contact between handler and pig was recorded. The Minimal treatment group was subjected to routine husbandry practices only. After 3 weeks of the handling treatments and tether-housing, all pigs were catheterized under full surgical anaesthesia. The pigs were allowed 4 days of recovery before collecting the following data: daytime plasma Cortisol concentration profiles, behavioural responses to a human in an arena test, Cortisol responses to human proximity, Cortisol responses to an A CTH-challenge and immunological responses to an injected mitogen.

In the Positive treatment, the amount of physical contact between pig and handler increased during the course of the experiment, while the amount of physical contact did not change in the Negative treatment. There were no effects of treatment on behavioural responses in the arena test. The average daytime concentration of free plasma Cortisol was lower in the Positive treatment than in the Negative or Minimal treatments. The Positive treatment also showed lower total and free plasma Cortisol concentrations pre- and posthuman proximity when compared with the Negative treatment. No differences were found between treatments in total and free plasma Cortisol concentrations following an ACTH challenge. The immunological response was greater in the Positive treatment compared with the Negative treatment and tended to be greater when compared with the Minimal treatment.

It was concluded that the nature of the human-animal relationship affected the physiological stress responses of pregnant pigs to tether-housing. Indications are that a positive human-animal relationship would obviate some of the negative effects of being kept in tether-stalls by lowering the basal cortisol concentration and by increasing immunological responsiveness.

Although human factors are recognized as influential factors affecting the welfare and productivity of farm animals, only limited research has been conducted to identify these important human characteristics and to quantify their effects. During the last 13 years we have studied two apparently important human factors: the attitude and the behaviour of stockpersons towards farm animals.

We have proposed that in intensive animal production systems there are some important sequential relationships between the attitude and behaviour of the stockperson towards farm animals and the behaviour, performance and welfare of farm animals. Basically we have suggested that because a stockperson's behaviour towards animals is largely under volitional control it is strongly influenced by the attitudes and beliefs that the stockperson holds about the animals. Furthermore, the stockperson's behaviour towards animals affects the animals’ fear of humans which, in turn, affects the animals’ productivity and welfare. It is the occurrence of a stress response by animals which are highly fearful of humans which places their productivity and welfare at risk We have published data which strongly support these interrelationships between human attitude and behaviour and animal behaviour, productivity and welfare. This paper reviews this and other research on this subject. The results of research in the pig industry and to a lesser extent, the poultry industries indicate the excellent opportunity which exists to improve animal productivity and welfare by training and selecting stockpersons to have desirable attitudinal and behavioural profiles towards farm animals.