Early Movement Matters: Examining the Influence of Early Postnatal Caregiving Experiences of Term Infants on Motor and Head Shape Outcomes Across Infancy

The nurturing, handling and positioning exposures infants experience during daily caregiving contribute to their physical, motor, cognitive and social–emotional development. A relationship exists between infant sleep and wake-time positioning, the emergence of motor skills and the development of head shape deformities diagnosed as non-synostotic plagiocephaly (NSP). However, the underlying causal mechanism of the specific caregiving behaviours that may play a role remains unclear. The purpose of the study was to investigate the association between maternal caregiving behaviours and the developmental outcomes of ‘low-risk’ term infants in the first 10 months of life. The first phase of the research involved the establishment of an expert panel of experienced clinical practitioners and researchers to design, construct and validate an observational scale—the Infant Handling Measure—to measure the physical capabilities of an adult to move, lift, hold, position and play with a young infant (neonate to four months) during regular infant caregiving activities. The second phase was an exploratory prospective longitudinal birth cohort study. Data were collected over eight collection points (three home-based and five online telephone sessions) to explore the patterns and possible mechanisms by which early infant caregiving exposures may influence the developmental outcomes of healthy ‘low-risk’ term infants. Observations of infant motor and head shape outcomes were obtained at one, three and 10 months, and observations of maternal–infant handling were obtained at one and three months. Self-reported parenting measures were collected at the eight time points, and infant caregiving measures were collected at the seven postnatal time points. A final sample of 48 ‘low-risk’ term singleton infant (24 male; 27 firstborn)–mother dyads completed all observational measures. Mothers had the strongest influence on infant motor and head shape outcomes. Maternal knowledge about infant development and insufficient parenting instruction on infant handling, positioning and care practices were found to be important factors influencing caregiving abilities. The number of adverse perinatal health events, knowledge of infant development and mothers’ early infant handling skills contributed to infant motor development. Risk analysis confirmed maternal knowledge of infant development, the consistent provision of centred head and body positions and the vi adoption of rotational movements in infant care activities were protective and reduced the risk of delayed motor development. Three factors contributed to adverse infant head shape outcomes: insufficient parenting instruction on infant care practices, infants spending more than 17 hours per day in supine position during the first six months of life and the late adoption of rotational movements in daily infant care routines. Risk analysis confirmed that prior learning of handling techniques and adopting rotational movements in infant care activities were protective and reduced the risk of NSP. Early mastery of infant handling by mothers in the first months of life may be a salient mechanism of protection for infant motor and head shape development. Low maternal knowledge about infant development and insufficient parenting instruction on infant care practices highlight the gaps in current parenting strategies. A collaborative revision of early infant handling education, including consumers and stakeholders, is recommended

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

The OMERACT Stepwise Approach to Select and Develop Imaging Outcome Measurement Instruments: The Musculoskeletal Ultrasound Example

Objective. To describe the Outcome Measures in Rheumatology (OMERACT) stepwise approach to select and develop an imaging instrument with musculoskeletal ultrasound (US) as an example. Methods. The OMERACT US Working Group (WG) developed a 4-step process to select instruments based on imaging. Step 1 applies the OMERACT Framework Instrument Selection Algorithm (OFISA) to existing US outcome measurement instruments for a specific indication. This step requires a literature review focused on the truth, discrimination, and feasibility aspects of the instrument for the target pathology. When the evidence is completely unsatisfactory, Step 2 is a consensus process to define the US characteristics of the target pathology including one or more so-called “elementary lesions”. Step 3 applies the agreed definitions to the image, evaluates their reliability, develops a severity grading of the lesion(s) at a given anatomical site, and evaluates the effect of the acquisition technique on feasibility and lesion(s) detection. Step 4 applies and assesses the definition(s) and scoring system(s) in cross-sectional studies and multicenter trials. The imaging instrument is now ready to pass a final OFISA check. Results. With this process in place, the US WG now has 18 subgroups developing US instruments in 10 different diseases. Half of them have passed Step 3, and the groups for enthesitis (spondyloarthritis, psoriatic arthritis), synovitis, and tenosynovitis (rheumatoid arthritis) have finished Step 4. Conclusion. The US WG approach to select and develop outcome measurement instruments based on imaging has been repeatedly and successfully applied in US, but is generic for imaging and fits with OMERACT Filter 2.1

Combining traditional dietary assessment methods with novel metabolomics techniques: present efforts by the Food Biomarker Alliance

FFQ, food diaries and 24 h recall methods represent the most commonly used dietary assessment tools in human studies on nutrition and health, but food intake biomarkers are assumed to provide a more objective reflection of intake. Unfortunately, very few of these biomarkers are sufficiently validated. This review provides an overview of food intake biomarker research and highlights present research efforts of the Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI-HDHL) Food Biomarkers Alliance (FoodBAll). In order to identify novel food intake biomarkers, the focus is on new food metabolomics techniques that allow the quantification of up to thousands of metabolites simultaneously, which may be applied in intervention and observational studies. As biomarkers are often influenced by various other factors than the food under investigation, FoodBAll developed a food intake biomarker quality and validity score aiming to assist the systematic evaluation of novel biomarkers. Moreover, to evaluate the applicability of nutritional biomarkers, studies are presently also focusing on associations between food intake biomarkers and diet-related disease risk. In order to be successful in these metabolomics studies, knowledge about available electronic metabolomics resources is necessary and further developments of these resources are essential. Ultimately, present efforts in this research area aim to advance quality control of traditional dietary assessment methods, advance compliance evaluation in nutritional intervention studies, and increase the significance of observational studies by investigating associations between nutrition and health

Phase 0 study of vandetanib-eluting radiopaque embolics as a pre-operative embolization treatment in patients with resectable liver malignancies

PURPOSE: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemo-embolization in patients with resectable liver malignancies. METHODS: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years, had resectable hepatocellular carcinoma (HCC)(Child-Pugh A) or colorectal liver metastases (mCRC). Patients received 1mL of BTG-002814 transarterially (containing 100mg vandetanib) 7-21 days prior to surgery. Primary objectives were to establish the safety and tolerability of BTG-002814, and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver post-treatment. Biomarker studies included circulating pro-angiogenic factors, perfusion computed tomography and dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI). RESULTS: Eight patients were enrolled: two with HCC, and six with mCRC. There was one Grade 3 adverse event (AE) pre-surgery and 18 post-surgery; six AEs were deemed BTG-002814 related. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days post-treatment with a mean maximum concentration (Cmax) of 24.3 ng/mL (SD 13.94) and present in resected liver tissue up to 32 days post-treatment (441-404,000 ng/g). Median tumor necrosis was 92.5% (range 5-100%). There were no significant changes in perfusion imaging parameters post-TACE. CONCLUSION: BTG-002814 has an acceptable safety profile in patients pre-surgery. Presence of vandetanib in tumor specimens up to 32 days post-treatment suggests sustained anticancer activity; low vandetanib plasma levels suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies