A cohort study of low birth weight and health outcomes in the first year of life, Ghana.

OBJECTIVE: To investigate the effect of birth weight on infant mortality, illness and care seeking in rural Ghana. METHODS: Using randomized controlled trial data, we compared infants weighing 2.00-2.49, 1.50-1.99 and < 1.50 kg with non-low-birth-weight infants. We generated adjusted mortality hazard ratios (aHR), adjusted illness rate ratios (aRR) and adjusted odds ratios (aOR) for health-facility admissions and absence of care seeking for four time periods: infancy, the neonatal period, early infancy and late infancy - represented by ages of 0-364, 0-27, 28-182 and 183-364 days, respectively. FINDINGS: Among 22 906 infants, compared with non-low-birth-weight infants: (i) infants weighing 2.00-2.49, 1.50-1.99 and < 1.50 kg were about two (aHR: 2.13; 95% confidence interval, CI: 1.76-2.59), eight (aHR: 8.21; 95% CI: 6.26-10.76) and 25 (aHR: 25.38; 95% CI: 18.36-35.10) times more likely to die in infancy, respectively; (ii) those born weighing < 1.50 kg were about 48 (aHR: 48.45; 95% CI: 32.81-71.55) and eight (aHR: 8.42; 95% CI: 3.09-22.92) times more likely to die in the neonatal period and late infancy, respectively; (iii) those born weighing 1.50-1.99 kg (aRR: 1.57; 95% CI: 1.27-1.95) or < 1.50 kg (aRR: 1.58; 95% CI: 1.13-2.21) had higher neonatal illness rates; and (iv) for those born weighing 1.50-1.99 kg, care was less likely to be sought in the neonatal period (aOR: 3.30; 95% CI: 1.98-5.48) and early infancy (aOR : 1.74; 95% CI: 1.26-2.39). CONCLUSION: For low-birth-weight infants in Ghana, strategies to minimize mortality and improve care seeking are needed

Neonatal vaccination of low birthweight infants in Ghana.

OBJECTIVES: Global vaccination policy advocates for identifying and targeting groups who are underserved by vaccination to increase equity and uptake. We investigated whether birth weight and other factors are determinants of neonatal BCG vaccination in order to identify infants underserved by vaccination. METHODS: We used logistic regression to calculate adjusted ORs (AORs) for the association between birth weight (categorised as non-low birth weight (NLBW) (≥2.50 kg) and low birth weight (LBW) (2-2.49 kg, 1.50-1.99 kg and 0.19). Facility-born infants were vaccinated at a mean of 6 days, suggesting that they were not vaccinated in the facility at birth but were referred for vaccination. CONCLUSIONS: LBW is a risk factor for neonatal under-vaccination, even for facility-born infants. Ensuring vaccination at facility births would substantively improve timing and equitable BCG vaccination

Novel application of behavioral assays allows dissociation of joint pathology from systemic extra-articular alterations induced by inflammatory arthritis

Introduction: Although rheumatoid arthritis (RA) is a disease of articular joints, patients often suffer from co-morbid neuropsychiatric changes, such as anxiety, that may reflect links between heightened systemic inflammation and abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Here, we apply behavioral neuroscience methods to assess the impact of antigen-induced arthritis (AIA) on behavioral performance in wild type (WT) and interleukin-10 deficient (Il10-/-) mice. Our aim was to identify limb-specific motor impairments, as well as neuropsychological responses to inflammatory arthritis. Methods: Behavioral testing was performed longitudinally in WT and Il10-/- mice before and after the induction of arthritic joint pathology. Footprint analysis, beam walking and open field assessment determined a range of motor, exploratory and anxiety-related parameters. Specific gene changes in HPA axis tissues were analyzed using qPCR. Results: Behavioral assessment revealed transient motor and exploratory impairments in mice receiving AIA, coinciding with joint swelling. Hind limb coordination deficits were independent of joint pathology. Behavioral impairments returned to baseline by 10 days post-AIA in WT mice. Il10-/- mice demonstrated comparable levels of swelling and joint pathology as WT mice up to 15 days post-AIA, but systemic differences were evident in mRNA expression in HPA axis tissues from Il10-/- mice post-AIA. Interestingly, the behavioral profile of Il10-/- mice revealed a significantly longer time post-AIA for activity and anxiety-related behaviors to recover. Conclusions: The novel application of sensitive behavioral tasks has enabled dissociation between behaviors that occur due to transient joint-specific pathology and those generated by more subtle systemic alterations that manifest post-AIA

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Are Ethnic and Gender Specific Equations Needed to Derive Fat Free Mass from Bioelectrical Impedance in Children of South Asian, Black African-Caribbean and White European Origin? Results of the Assessment of Body Composition in Children Study

Background Bioelectrical impedance analysis (BIA) is a potentially valuable method for assessing lean mass and body fat levels in children from different ethnic groups. We examined the need for ethnic- and gender-specific equations for estimating fat free mass (FFM) from BIA in children from different ethnic groups and examined their effects on the assessment of ethnic differences in body fat. Methods Cross-sectional study of children aged 8–10 years in London Primary schools including 325 South Asians, 250 black African-Caribbeans and 289 white Europeans with measurements of height, weight and arm-leg impedance (Z; Bodystat 1500). Total body water was estimated from deuterium dilution and converted to FFM. Multilevel models were used to derive three types of equation {A: FFM = linear combination(height+weight+Z); B: FFM = linear combination(height2/Z); C: FFM = linear combination(height2/Z+weight)}. Results Ethnicity and gender were important predictors of FFM and improved model fit in all equations. The models of best fit were ethnicity and gender specific versions of equation A, followed by equation C; these provided accurate assessments of ethnic differences in FFM and FM. In contrast, the use of generic equations led to underestimation of both the negative South Asian-white European FFM difference and the positive black African-Caribbean-white European FFM difference (by 0.53 kg and by 0.73 kg respectively for equation A). The use of generic equations underestimated the positive South Asian-white European difference in fat mass (FM) and overestimated the positive black African-Caribbean-white European difference in FM (by 4.7% and 10.1% respectively for equation A). Consistent results were observed when the equations were applied to a large external data set. Conclusions Ethnic- and gender-specific equations for predicting FFM from BIA provide better estimates of ethnic differences in FFM and FM in children, while generic equations can misrepresent these ethnic differences

Reducing Opioid Use for Chronic Pain With a Group-Based Intervention: A Randomized Clinical Trial

IMPORTANCE: Opioid use for chronic nonmalignant pain can be harmful. OBJECTIVE: To test whether a multicomponent, group-based, self-management intervention reduced opioid use and improved pain-related disability compared with usual care. DESIGN, SETTING, AND PARTICIPANTS: Multicentered, randomized clinical trial of 608 adults taking strong opioids (buprenorphine, dipipanone, morphine, diamorphine, fentanyl, hydromorphone, methadone, oxycodone, papaveretum, pentazocine, pethidine, tapentadol, and tramadol) to treat chronic nonmalignant pain. The study was conducted in 191 primary care centers in England between May 17, 2017, and January 30, 2019. Final follow-up occurred March 18, 2020. INTERVENTION: Participants were randomized 1:1 to either usual care or 3-day-long group sessions that emphasized skill-based learning and education, supplemented by 1-on-1 support delivered by a nurse and lay person for 12 months. MAIN OUTCOMES AND MEASURES: The 2 primary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference Short Form 8a (PROMIS-PI-SF-8a) score (T-score range, 40.7-77; 77 indicates worst pain interference; minimal clinically important difference, 3.5) and the proportion of participants who discontinued opioids at 12 months, measured by self-report. RESULTS: Of 608 participants randomized (mean age, 61 years; 362 female [60%]; median daily morphine equivalent dose, 46 mg [IQR, 25 to 79]), 440 (72%) completed 12-month follow-up. There was no statistically significant difference in PROMIS-PI-SF-8a scores between the 2 groups at 12-month follow-up (-4.1 in the intervention and -3.17 in the usual care groups; between-group difference: mean difference, -0.52 [95% CI, -1.94 to 0.89]; P = .15). At 12 months, opioid discontinuation occurred in 65 of 225 participants (29%) in the intervention group and 15 of 208 participants (7%) in the usual care group (odds ratio, 5.55 [95% CI, 2.80 to 10.99]; absolute difference, 21.7% [95% CI, 14.8% to 28.6%]; P < .001). Serious adverse events occurred in 8% (25/305) of the participants in the intervention group and 5% (16/303) of the participants in the usual care group. The most common serious adverse events were gastrointestinal (2% in the intervention group and 0% in the usual care group) and locomotor/musculoskeletal (2% in the intervention group and 1% in the usual care group). Four people (1%) in the intervention group received additional medical care for possible or probable symptoms of opioid withdrawal (shortness of breath, hot flushes, fever and pain, small intestinal bleed, and an overdose suicide attempt). CONCLUSIONS AND RELEVANCE: In people with chronic pain due to nonmalignant causes, compared with usual care, a group-based educational intervention that included group and individual support and skill-based learning significantly reduced patient-reported use of opioids, but had no effect on perceived pain interference with daily life activities. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN49470934

ADP-Ribosylation Factor 6 Expression and Activation Are Reduced in Myometrium in Complicated Pregnancies

ARF6 (ADP-ribosylation factor 6) small GTP binding protein plays critical roles in actin cytoskeleton rearrangements and membrane trafficking, including internalisation of G protein coupled receptors (GPCR). ARF6 operates by cycling between GDP-bound (inactive) and GTP-bound (active) forms and is a potential regulator of GPCR-mediated uterine activity during pregnancy and labour. ARF6 contains very low intrinsic GTP binding activity and depends on GEFs (guanine nucleotide exchange factors) such as CYTH3 (cytohesin 3) to bind GTP. ARF6 and CYTH3 were originally cloned from human placenta, but there is no information on their expression in other reproductive tissues.The expression of ARF6, ARF1, and CYTH1-4 was investigated by measuring mRNA (using RT-PCR) and protein levels (using immunoblotting) in samples of myometrium obtained from non-pregnant women, and women with normal pregnancies, before or after the spontaneous onset of labour. We also analysed myometrial samples from women with spontaneous preterm labour and from women with complicated pregnancies requiring emergency preterm delivery. The GST)-effector pull down assay was used to study the presence of active ARF6 and ARF1 in all myometrial extracts.ARF6, ARF1 and CYTH3 but not CYTH1, CYTH2 and CYTH4 were expressed in all samples and the levels did not change with pregnancy or labour. However, ARF6 and CYTH3 but not ARF1 levels were significantly reduced in complicated pregnancies. The alterations in the expression of ARF6 and its GEF in human myometrium indicate a potential involvement of this signalling system in modulating the response of myometrial smooth muscle in complicated pregnancies. The levels of ARF6-GTP or ARF1-GTP did not change with pregnancy or labour but ARF6-GTP levels were significantly decreased in women with severe complications of pregnancy.We have demonstrated a functional ARF6 system in human myometrium and a correlation between ARF6 level and activity in uterine and abnormal pregnancy

A supportive self-management program for people with chronic headaches and migraine : a randomized controlled trial and economic evaluation

Background and Objectives: Chronic headache disorders are a major cause of pain and disability. Education and supportive self-management approaches could reduce burden of headache disability. We tested the effectiveness of a group educational and supportive self-management programme for people living with chronic headaches. Methods: A pragmatic randomised controlled trial. Participants were aged ≥18 years with chronic migraine or chronic tension type headache, with or without medication overuse headache. We primarily recruited from general practices. Participants were assigned to either a two-day group education and self-management programme, a one-to-one nurse interview, and telephone support or to usual care plus relaxation material. The primary outcome was headache related quality of life using the Headache Impact Test (HIT-6) at 12 months. The primary analysis used intention-to-treat principles for participants with migraine and both baseline and 12-month HIT-6 data. Results: Between April 2017 and March 2019, we randomised 736 participants. Since only nine participants just had tension type headache our main analyses were on the 727 participants with migraine. Of these 376 were allocated to the self-management intervention 351 to usual care. Data from 586 (81%) participants were analysed for primary outcome. There was no between group difference in HIT-6, (adjusted mean difference = -0·3, 95% CI -1·23 to 0·67), or headache days (0·9, 95% CI -0·29, 2·05), at 12 months. The CHESS intervention generated incremental adjusted costs of £268 (95% CI,£176 to £377) [USD383 (95%CI USD252 to USD539)] and incremental adjusted quality-adjusted life years (QALYs) of 0.031 (95% CI -0.005 to .063). The incremental cost-effectiveness ratio was £8,617 (USD12,322) per QALY gained. Discussion: These findings conclusively show a lack of benefit for quality of life or monthly headache days from a brief group education and supportive self-management programme for people living with chronic migraine or chronic tension type headache with episodic migraine. Registered on the International Standard Randomized Controlled Trial Number registry, ISRCTN79708100 16th December 2015 https://doi.org/10.1186/ISRCTN79708100 The first enrolment was 24th April 2017. Classification of evidence: This study provides Class III evidence that a brief group education and self-management program does not increase the probability of improvement in headache related quality of life in people with chronic migraine

Reducing opioid use for chronic pain with a group-based intervention

Importance Opioid use for chronic nonmalignant pain can be harmful. Objective To test whether a multicomponent, group-based, self-management intervention reduced opioid use and improved pain-related disability compared with usual care. Design, Setting, and Participants Multicentered, randomized clinical trial of 608 adults taking strong opioids (buprenorphine, dipipanone, morphine, diamorphine, fentanyl, hydromorphone, methadone, oxycodone, papaveretum, pentazocine, pethidine, tapentadol, and tramadol) to treat chronic nonmalignant pain. The study was conducted in 191 primary care centers in England between May 17, 2017, and January 30, 2019. Final follow-up occurred March 18, 2020. Intervention Participants were randomized 1:1 to either usual care or 3-day–long group sessions that emphasized skill-based learning and education, supplemented by 1-on-1 support delivered by a nurse and lay person for 12 months. Main Outcomes and Measures The 2 primary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference Short Form 8a (PROMIS-PI-SF-8a) score (T-score range, 40.7-77; 77 indicates worst pain interference; minimal clinically important difference, 3.5) and the proportion of participants who discontinued opioids at 12 months, measured by self-report. Results Of 608 participants randomized (mean age, 61 years; 362 female [60%]; median daily morphine equivalent dose, 46 mg [IQR, 25 to 79]), 440 (72%) completed 12-month follow-up. There was no statistically significant difference in PROMIS-PI-SF-8a scores between the 2 groups at 12-month follow-up (−4.1 in the intervention and −3.17 in the usual care groups; between-group difference: mean difference, −0.52 [95% CI, −1.94 to 0.89]; P = .15). At 12 months, opioid discontinuation occurred in 65 of 225 participants (29%) in the intervention group and 15 of 208 participants (7%) in the usual care group (odds ratio, 5.55 [95% CI, 2.80 to 10.99]; absolute difference, 21.7% [95% CI, 14.8% to 28.6%]; P < .001). Serious adverse events occurred in 8% (25/305) of the participants in the intervention group and 5% (16/303) of the participants in the usual care group. The most common serious adverse events were gastrointestinal (2% in the intervention group and 0% in the usual care group) and locomotor/musculoskeletal (2% in the intervention group and 1% in the usual care group). Four people (1%) in the intervention group received additional medical care for possible or probable symptoms of opioid withdrawal (shortness of breath, hot flushes, fever and pain, small intestinal bleed, and an overdose suicide attempt). Conclusions and Relevance In people with chronic pain due to nonmalignant causes, compared with usual care, a group-based educational intervention that included group and individual support and skill-based learning significantly reduced patient-reported use of opioids, but had no effect on perceived pain interference with daily life activities. Trial Registration isrctn.org Identifier: ISRCTN4947093