A Systematic Review With Pairwise and Network Meta-analysis of Closed Reduction Methods for Anterior Shoulder Dislocation.

STUDY OBJECTIVE: To review closed reduction methods for anterior shoulder dislocation and perform the first comprehensive comparison of the individual methods in terms of success rate, pain, and reduction time. METHODS: We searched MEDLINE, PubMed, EMBASE, Cochrane, and ClinicalTrials.gov for randomized controlled trials registered until December 31, 2020. We performed a pairwise and network meta-analysis using a Bayesian random-effects model. Two authors independently performed screening and risk-of-bias assessment. RESULTS: We found 14 studies with 1,189 patients. In a pairwise meta-analysis, no significant difference was found in the only comparable pair, namely, the Kocher method versus the Hippocratic method (success rate: odds ratio, 1.21; 95% confidence interval [CI], 0.53, 2.75: pain during reduction [visual analog scale]: standard mean difference, -0.33; 95% CI, -0.69, 0.02; reduction time [minutes]: mean difference, 0.19, 95% CI, -1.77, 2.15). In network meta-analysis, FARES (Fast, Reliable, and Safe) was the only method significantly less painful than the Kocher method (mean difference, -4.0; 95% credible interval, -7.6, -0.40). In the surface under the cumulative ranking (SUCRA) plot of success rate, FARES, and the Boss-Holzach-Matter/Davos method showed high values. For pain during reduction, FARES had the highest SUCRA value in the overall analysis. In the SUCRA plot of reduction time, modified external rotation and FARES had high values. The only complication was 1 case of fracture with the Kocher method. CONCLUSION: Overall, Boss-Holzach-Matter/Davos, and FARES demonstrated the most favorable value for success rates, whereas both FARES and modified external rotation were more favorable in reduction times. FARES had the most favorable SUCRA for pain during reduction. Future work directly comparing techniques is needed to better understand the difference in reduction success and complications.

Resolving titin's lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes.

Cardiac protein homeostasis, sarcomere assembly, and integration of titin as the sarcomeric backbone are tightly regulated to facilitate adaptation and repair. Very little is known on how the >3-MDa titin protein is synthesized, moved, inserted into sarcomeres, detached, and degraded. Here, we generated a bifluorescently labeled knockin mouse to simultaneously visualize both ends of the molecule and follow titin's life cycle in vivo. We find titin mRNA, protein synthesis and degradation compartmentalized toward the Z-disk in adult, but not embryonic cardiomyocytes. Originating at the Z-disk, titin contributes to a soluble protein pool (>15% of total titin) before it is integrated into the sarcomere lattice. Titin integration, disintegration, and reintegration are stochastic and do not proceed sequentially from Z-disk to M-band, as suggested previously. Exchange between soluble and integrated titin depends on titin protein composition and differs between individual cardiomyocytes. Thus, titin dynamics facilitate embryonic vs. adult sarcomere remodeling with implications for cardiac development and disease.

Nutrition-specific interventions for preventing and controlling anaemia throughout the life cycle: an overview of systematic reviews.

BACKGROUND: Anaemia is a prevalent health problem worldwide. Some types are preventable or controllable with iron supplementation (pills or drops), fortification (sprinkles or powders containing iron added to food) or improvements to dietary diversity and quality (e.g. education or counselling). OBJECTIVES: To summarise the evidence from systematic reviews regarding the benefits or harms of nutrition-specific interventions for preventing and controlling anaemia in anaemic or non-anaemic, apparently healthy populations throughout the life cycle. METHODS: In August 2020, we searched MEDLINE, Embase and 10 other databases for systematic reviews of randomised controlled trials (RCTs) in anaemic or non-anaemic, apparently healthy populations. We followed standard Cochrane methodology, extracting GRADE ratings where provided. The primary outcomes were haemoglobin (Hb) concentration, anaemia, and iron deficiency anaemia (IDA); secondary outcomes were iron deficiency (ID), severe anaemia and adverse effects (e.g. diarrhoea, vomiting). MAIN RESULTS: We included 75 systematic reviews, 33 of which provided GRADE assessments; these varied between high and very low. Infants (6 to 23 months; 13 reviews) Iron supplementation increased Hb levels and reduced the risk of anaemia and IDA in two reviews. Iron fortification of milk or cereals, multiple-micronutrient powder (MMNP), home fortification of complementary foods, and supplementary feeding increased Hb levels and reduced the risk of anaemia in six reviews. In one review, lipid-based nutrient supplementation (LNS) reduced the risk of anaemia. In another, caterpillar cereal increased Hb levels and IDA prevalence. Food-based strategies (red meat and fortified cow's milk, beef) showed no evidence of a difference (1 review). Preschool and school-aged children (2 to 10 years; 8 reviews) Daily or intermittent iron supplementation increased Hb levels and reduced the risk of anaemia and ID in two reviews. One review found no evidence of difference in Hb levels, but an increased risk of anaemia and ID for the intermittent regime. All suggested that zinc plus iron supplementation versus zinc alone, multiple-micronutrient (MMN)-fortified beverage versus control, and point-of-use fortification of food with iron-containing micronutrient powder (MNP) versus placebo or no intervention may increase Hb levels and reduce the risk of anaemia and ID. Fortified dairy products and cereal food showed no evidence of a difference on the incidence of anaemia (1 review). Adolescent children (11 to 18 years; 4 reviews) Compared with no supplementation or placebo, five types of iron supplementation may increase Hb levels and reduce the risk of anaemia (3 reviews). One review on prevention found no evidence of a difference in anaemia incidence on iron supplementation with or without folic acid, but Hb levels increased. Another suggested that nutritional supplementation and counselling reduced IDA. One review comparing MMN fortification with no fortification observed no evidence of a difference in Hb levels. Non-pregnant women of reproductive age (19 to 49 years; 5 reviews) Two reviews suggested that iron therapy (oral, intravenous (IV), intramuscular (IM)) increased Hb levels; one showed that iron folic acid supplementation reduced anaemia incidence; and another that daily iron supplementation with or without folic acid or vitamin C increased Hb levels and reduced the risk of anaemia and ID. No review reported interventions related to fortification or dietary diversity and quality. Pregnant women of reproductive age (15 to 49 years; 23 reviews) One review apiece suggested that: daily iron supplementation with or without folic acid increased Hb levels in the third trimester or at delivery and in the postpartum period, and reduced the risk of anaemia, IDA and ID in the third trimester or at delivery; intermittent iron supplementation had no effect on Hb levels and IDA, but increased the risk of anaemia at or near term and ID, and reduced the risk of side effects; vitamin A supplementation alone versus placebo, no intervention or other micronutrient might increase maternal Hb levels and reduce the risk of maternal anaemia; MMN with iron and folic acid versus placebo reduced the risk of anaemia; supplementation with oral bovine lactoferrin versus oral ferrous iron preparations increased Hb levels and reduced gastrointestinal side effects; MNP for point-of-use fortification of food versus iron and folic acid supplementation might decrease Hb levels at 32 weeks' gestation and increase the risk of anaemia; and LNS versus iron or folic acid and MMN increased the risk of anaemia. Mixed population (all ages; 22 reviews) Iron supplementation versus placebo or control increased Hb levels in healthy children, adults, and elderly people (4 reviews). Hb levels appeared to increase and risk of anaemia and ID decrease in two reviews investigating MMN fortification versus placebo or no treatment, iron fortified flour versus control, double fortified salt versus iodine only fortified salt, and rice fortification with iron alone or in combination with other micronutrients versus unfortified rice or no intervention. Each review suggested that fortified versus non-fortified condiments or noodles, fortified (sodium iron ethylenediaminetetraacetate; NaFeEDTA) versus non-fortified soy sauce, and double-fortified salt versus control salt may increase Hb concentration and reduce the risk of anaemia. One review indicated that Hb levels increased for children who were anaemic or had IDA and received iron supplementation, and decreased for those who received dietary interventions. Another assessed the effects of foods prepared in iron pots, and found higher Hb levels in children with low-risk malaria status in two trials, but no difference when comparing food prepared in non-cast iron pots in a high-risk malaria endemicity mixed population. There was no evidence of a difference for adverse effects. Anaemia and malaria prevalence were rarely reported. No review focused on women aged 50 to 65 years plus or men (19 to 65 years plus). AUTHORS' CONCLUSIONS: Compared to no treatment, daily iron supplementation may increase Hb levels and reduce the risk of anaemia and IDA in infants, preschool and school-aged children and pregnant and non-pregnant women. Iron fortification of foods in infants and use of iron pots with children may have prophylactic benefits for malaria endemicity low-risk populations. In any age group, only a limited number of reviews assessed interventions to improve dietary diversity and quality. Future trials should assess the effects of these types of interventions, and consider the requirements of different populations.

Skin preparation for preventing infection following caesarean section.

BACKGROUND: The risk of maternal mortality and morbidity is higher after caesarean section than for vaginal birth. With increasing rates of caesarean section, it is important to minimise risks to the mother as much as possible. This review focused on different skin preparations to prevent infection. This is an update of a review last published in 2018. OBJECTIVES: To compare the effects of different antiseptic agents, different methods of application, or different forms of antiseptic used for preoperative skin preparation for preventing postcaesarean infection. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 July 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised trials, evaluating any type of preoperative skin preparation (agents, methods or forms). We included studies presented only as abstracts, if there was enough information to assess risk of bias. Comparisons of interest in this review were between: different antiseptic agents (e.g. alcohol, povidone iodine), different methods of antiseptic application (e.g. scrub, paint, drape), different forms of antiseptic (e.g. powder, liquid), and also between different packages of skin preparation including a mix of agents and methods, such as a plastic incisional drape, which may or may not be impregnated with antiseptic agents. We mainly focused on the comparison between different agents, with and without the use of drapes. Only studies involving the preparation of the incision area were included. This review did not cover studies of preoperative handwashing by the surgical team or preoperative bathing. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed all potential studies for inclusion, assessed risk of bias, extracted the data and checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 13 individually-randomised controlled trials (RCTs), with a total of 6938 women who were undergoing caesarean section. Twelve trials (6916 women) contributed data to this review. The trial dates ranged from 1983 to 2016. Six trials were conducted in the USA, and the remainder in India, Egypt, Nigeria, South Africa, France, Denmark, and Indonesia. The included studies were broadly at low risk of bias for most domains, although high risk of detection bias raised some specific concerns in a number of studies. Length of stay was only reported in one comparison. Antiseptic agents Parachlorometaxylenol with iodine versus iodine alone We are uncertain whether parachlorometaxylenol with iodine made any difference to the incidence of surgical site infection (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.04 to 2.99; 1 trial, 50 women), or endometritis (RR 0.88, 95% CI 0.56 to 1.38; 1 trial, 50 women) when compared with iodine alone, because the certainty of the evidence was very low. Adverse events (maternal or neonatal) were not reported. Chlorhexidine gluconate versus povidone iodine Moderate-certainty evidence suggested that chlorhexidine gluconate, when compared with povidone iodine, probably slightly reduces the incidence of surgical site infection (RR 0.72, 95% CI 0.58 to 0.91; 8 trials, 4323 women). This effect was still present in a sensitivity analysis after removing four trials at high risk of bias for outcome assessment (RR 0.87, 95% CI 0.62 to 1.23; 4 trials, 2037 women). Low-certainty evidence indicated that chlorhexidine gluconate, when compared with povidone iodine, may make little or no difference to the incidence of endometritis (RR 0.95, 95% CI 0.49 to 1.86; 3 trials, 2484 women). It is uncertain whether chlorhexidine gluconate reduces maternal skin irritation or allergic skin reaction (RR 0.64, 95% CI 0.28 to 1.46; 3 trials, 1926 women; very low certainty evidence). One small study (60 women) reported reduced bacterial growth at 18 hours after caesarean section for women who had chlorhexidine gluconate preparation compared with women who had povidone iodine preparation (RR 0.23, 95% CI 0.07 to 0.70). Methods Drape versus no drape This comparison investigated the use of drape versus no drape, following preparation of the skin with antiseptics. Low-certainty evidence suggested that using a drape before surgery compared with no drape, may make little or no difference to the incidence of surgical site infection (RR 1.29, 95% confidence interval (CI) 0.97 to 1.71; 3 trials, 1373 women), and probably makes little or no difference to the length of stay in the hospital (mean difference (MD) 0.10 days, 95% CI -0.27 to 0.46; 1 trial, 603 women; moderate-certainty evidence). One trial compared an alcohol scrub and iodophor drape with a five-minute iodophor scrub only, and reported no surgical site infection in either group (79 women, very-low certainty evidence). We were uncertain whether the combination of a one-minute alcohol scrub and a drape reduced the incidence of metritis when compared with a five-minute scrub, because the certainty of the evidence was very low (RR 1.62, 95% CI 0.29 to 9.16; 1 trial, 79 women). The studies did not report on adverse events (maternal or neonatal). AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that preparing the skin with chlorhexidine gluconate before caesarean section is probably slightly more effective at reducing the incidence of surgical site infection in comparison to povidone iodine. For other outcomes examined there was insufficient evidence available from the included RCTs. Most of the evidence in this review was deemed to be very low or low certainty. This means that for most findings, our confidence in any evidence of an intervention effect is limited, and indicates the need for more high-quality research. Therefore, it is not yet clear what sort of skin preparation may be most effective for preventing postcaesarean surgical site infection, or for reducing other undesirable outcomes for mother and baby. Well-designed RCTs, with larger sample sizes are needed. High-priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), and application methods (scrubbing, swabbing, or draping). We found two studies that are ongoing; we will incorporate the results of these studies in future updates of this review.

Antenatal interventions for preventing stillbirth, fetal loss and perinatal death: an overview of Cochrane systematic reviews.

BACKGROUND: Stillbirth is generally defined as a death prior to birth at or after 22 weeks' gestation. It remains a major public health concern globally. Antenatal interventions may reduce stillbirths and improve maternal and neonatal outcomes in settings with high rates of stillbirth. There are several key antenatal strategies that aim to prevent stillbirth including nutrition, and prevention and management of infections. OBJECTIVES: To summarise the evidence from Cochrane systematic reviews on the effects of antenatal interventions for preventing stillbirth for low risk or unselected populations of women. METHODS: We collaborated with Cochrane Pregnancy and Childbirth's Information Specialist to identify all their published reviews that specified or reported stillbirth; and we searched the Cochrane Database of Systematic Reviews (search date: 29 Feburary 2020) to identify reviews published within other Cochrane groups. The primary outcome measure was stillbirth but in the absence of stillbirth data, we used perinatal mortality (both stillbirth and death in the first week of life), fetal loss or fetal death as outcomes. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. We assigned interventions to categories with graphic icons to classify the effectiveness of interventions as: clear evidence of benefit or harm; clear evidence of no effect or equivalence; possible benefit or harm; or unknown benefit or harm or no effect or equivalence. MAIN RESULTS: We identified 43 Cochrane Reviews that included interventions in pregnant women with the potential for preventing stillbirth; all of the included reviews reported our primary outcome 'stillbirth' or in the absence of stillbirth, 'perinatal death' or 'fetal loss/fetal death'. AMSTAR quality was high in 40 reviews with scores ranging from 8 to 11 and moderate in three reviews with a score of 7. Nutrition interventions Clear evidence of benefit: balanced energy/protein supplementation versus no supplementation suggests a probable reduction in stillbirth (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.39 to 0.94, 5 randomised controlled trials (RCTs), 3408 women; moderate-certainty evidence). Clear evidence of no effect or equivalence for stillbirth or perinatal death: vitamin A alone versus placebo or no treatment; and multiple micronutrients with iron and folic acid versus iron with or without folic acid. Unknown benefit or harm or no effect or equivalence: for all other nutrition interventions examined the effects were uncertain. Prevention and management of infections Possible benefit for fetal loss or death: insecticide-treated anti-malarial nets versus no nets (RR 0.67, 95% CI 0.47 to 0.97, 4 RCTs; low-certainty). Unknown evidence of no effect or equivalence: drugs for preventing malaria (stillbirth RR 1.02, 95% CI 0.76 to 1.36, 5 RCTs, 7130 women, moderate certainty in women of all parity; perinatal death RR 1.24, 95% CI 0.94 to 1.63, 4 RCTs, 5216 women, moderate-certainty in women of all parity). Prevention, detection and management of other morbidities Clear evidence of benefit: the following interventions suggest a reduction: midwife-led models of care in settings where the midwife is the primary healthcare provider particularly for low-risk pregnant women (overall fetal loss/neonatal death reduction RR 0.84, 95% CI 0.71 to 0.99, 13 RCTs, 17,561 women; high-certainty), training versus not training traditional birth attendants in rural populations of low- and middle-income countries (stillbirth reduction odds ratio (OR) 0.69, 95% CI 0.57 to 0.83, 1 RCT, 18,699 women, moderate-certainty; perinatal death reduction OR 0.70, 95% CI 0.59 to 0.83, 1 RCT, 18,699 women, moderate-certainty). Clear evidence of harm: a reduced number of antenatal care visits probably results in an increase in perinatal death (RR 1.14 95% CI 1.00 to 1.31, 5 RCTs, 56,431 women; moderate-certainty evidence). Clear evidence of no effect or equivalence: there was evidence of no effect in the risk of stillbirth/fetal loss or perinatal death for the following interventions and comparisons: psychosocial interventions; and providing case notes to women. Possible benefit: community-based intervention packages (including community support groups/women's groups, community mobilisation and home visitation, or training traditional birth attendants who made home visits) may result in a reduction of stillbirth (RR 0.81, 95% CI 0.73 to 0.91, 15 RCTs, 201,181 women; low-certainty) and perinatal death (RR 0.78, 95% CI 0.70 to 0.86, 17 RCTs, 282,327 women; low-certainty). Unknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined. Screening and management of fetal growth and well-being Clear evidence of benefit: computerised antenatal cardiotocography for assessing infant's well-being in utero compared with traditional antenatal cardiotocography (perinatal mortality reduction RR 0.20, 95% CI 0.04 to 0.88, 2 RCTs, 469 women; moderate-certainty). Unknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined. AUTHORS' CONCLUSIONS: While most interventions were unable to demonstrate a clear effect in reducing stillbirth or perinatal death, several interventions suggested a clear benefit, such as balanced energy/protein supplements, midwife-led models of care, training versus not training traditional birth attendants, and antenatal cardiotocography. Possible benefits were also observed for insecticide-treated anti-malarial nets and community-based intervention packages, whereas a reduced number of antenatal care visits were shown to be harmful. However, there was variation in the effectiveness of interventions across different settings, indicating the need to carefully understand the context in which these interventions were tested. Further high-quality RCTs are needed to evaluate the effects of antenatal preventive interventions and which approaches are most effective to reduce the risk of stillbirth. Stillbirth (or fetal death), perinatal and neonatal death need to be reported separately in future RCTs of antenatal interventions to allow assessment of different interventions on these rare but important outcomes and they need to clearly define the target populations of women where the intervention is most likely to be of benefit. As the high burden of stillbirths occurs in low- and middle-income countries, further high-quality trials need to be conducted in these settings as a priority.

Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age.

BACKGROUND: Vitamin and mineral deficiencies, particularly those of iron, vitamin A, and zinc, affect more than two billion people worldwide. Young children are highly vulnerable because of rapid growth and inadequate dietary practices. Multiple micronutrient powders (MNPs) are single-dose packets containing multiple vitamins and minerals in powder form, which are mixed into any semi-solid food for children six months of age or older. The use of MNPs for home or point-of-use fortification of complementary foods has been proposed as an intervention for improving micronutrient intake in children under two years of age. In 2014, MNP interventions were implemented in 43 countries and reached over three million children. This review updates a previous Cochrane Review, which has become out-of-date. OBJECTIVES: To assess the effects and safety of home (point-of-use) fortification of foods with MNPs on nutrition, health, and developmental outcomes in children under two years of age. For the purposes of this review, home fortification with MNP refers to the addition of powders containing vitamins and minerals to semi-solid foods immediately before consumption. This can be done at home or at any other place that meals are consumed (e.g. schools, refugee camps). For this reason, MNPs are also referred to as point-of-use fortification. SEARCH METHODS: We searched the following databases up to July 2019: CENTRAL, MEDLINE, Embase, and eight other databases. We also searched four trials registers, contacted relevant organisations and authors of included studies to identify any ongoing or unpublished studies, and searched the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs with individual randomisation or cluster-randomisation. Participants were infants and young children aged 6 to 23 months at the time of intervention, with no identified specific health problems. The intervention consisted of consumption of food fortified at the point of use with MNP formulated with at least iron, zinc, and vitamin A, compared with placebo, no intervention, or use of iron-containing supplements, which is standard practice. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, and assessed the risk of bias of included studies. We reported categorical outcomes as risk ratios (RRs) or odds ratios (ORs), with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) and 95% CIs. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 29 studies (33,147 children) conducted in low- and middle-income countries in Asia, Africa, Latin America, and the Caribbean, where anaemia is a public health problem. Twenty-six studies with 27,051 children contributed data. The interventions lasted between 2 and 44 months, and the powder formulations contained between 5 and 22 nutrients. Among the 26 studies contributing data, 24 studies (26,486 children) compared the use of MNP versus no intervention or placebo; the two remaining studies compared the use of MNP versus an iron-only supplement (iron drops) given daily. The main outcomes of interest were related to anaemia and iron status. We assessed most of the included studies at low risk of selection and attrition bias. We considered some studies to be at high risk of performance and detection bias due to lack of blinding. Most studies were funded by government programmes or foundations; only two were funded by industry. Home fortification with MNP, compared with no intervention or placebo, reduced the risk of anaemia in infants and young children by 18% (RR 0.82, 95% CI 0.76 to 0.90; 16 studies; 9927 children; moderate-certainty evidence) and iron deficiency by 53% (RR 0.47, 95% CI 0.39 to 0.56; 7 studies; 1634 children; high-certainty evidence). Children receiving MNP had higher haemoglobin concentrations (MD 2.74 g/L, 95% CI 1.95 to 3.53; 20 studies; 10,509 children; low-certainty evidence) and higher iron status (MD 12.93 µg/L, 95% CI 7.41 to 18.45; 7 studies; 2612 children; moderate-certainty evidence) at follow-up compared with children receiving the control intervention. We did not find an effect on weight-for-age (MD 0.02, 95% CI -0.03 to 0.07; 10 studies; 9287 children; moderate-certainty evidence). Few studies reported morbidity outcomes (three to five studies each outcome) and definitions varied, but MNP did not increase diarrhoea, upper respiratory infection, malaria, or all-cause morbidity. In comparison with daily iron supplementation, the use of MNP produced similar results for anaemia (RR 0.89, 95% CI 0.58 to 1.39; 1 study; 145 children; low-certainty evidence) and haemoglobin concentrations (MD -2.81 g/L, 95% CI -10.84 to 5.22; 2 studies; 278 children; very low-certainty evidence) but less diarrhoea (RR 0.52, 95% CI 0.38 to 0.72; 1 study; 262 children; low-certainty of evidence). However, given the limited quantity of data, these results should be interpreted cautiously. Reporting of death was infrequent, although no trials reported deaths attributable to the intervention. Information on side effects and morbidity, including malaria and diarrhoea, was scarce. It appears that use of MNP is efficacious among infants and young children aged 6 to 23 months who are living in settings with different prevalences of anaemia and malaria endemicity, regardless of intervention duration. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups. AUTHORS' CONCLUSIONS: Home fortification of foods with MNP is an effective intervention for reducing anaemia and iron deficiency in children younger than two years of age. Providing MNP is better than providing no intervention or placebo and may be comparable to using daily iron supplementation. The benefits of this intervention as a child survival strategy or for developmental outcomes are unclear. Further investigation of morbidity outcomes, including malaria and diarrhoea, is needed. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups.

Improving Patients' Medication Adherence and Outcomes in Nonhospital Settings Through eHealth: Systematic Review of Randomized Controlled Trials.

BACKGROUND: Electronic health (eHealth) refers to the use of information and communication technologies for health. It plays an increasingly important role in patients' medication management. OBJECTIVE: To assess evidence on (1) whether eHealth for patients' medication management can improve drug adherence and health outcomes in nonhospital settings and (2) which eHealth functions are commonly used and are effective in improving drug adherence. METHODS: We searched for randomized controlled trials (RCTs) on PubMed, MEDLINE, CINAHL, EMBASE, EmCare, ProQuest, Scopus, Web of Science, ScienceDirect, and IEEE Xplore, in addition to other published sources between 2000 and 2018. We evaluated the studies against the primary outcome measure of medication adherence and multiple secondary health care outcome measures relating to adverse events, quality of life, patient satisfaction, and health expenditure. The quality of the studies included was assessed using the Cochrane Collaboration's Risk of Bias (RoB) tool. RESULTS: Our initial search yielded 9909 records, and 24 studies met the selection criteria. Of these, 13 indicated improvement in medication adherence at the significance level of P<.1 and 2 indicated an improved quality of life at the significance level of P<.01. The top 3 functions that were employed included mechanisms to communicate with caregivers, monitoring health features, and reminders and alerts. eHealth functions of providing information and education, and dispensing treatment and administration support tended to favor improved medication adherence outcomes (Fisher exact test, P=.02). There were differences in the characteristics of the study population, intervention design, functionality provided, reporting adherence, and outcome measures among the included studies. RoB assessment items, including blinding of outcome assessment and method for allocation concealment, were not explicitly reported in a large number of studies. CONCLUSIONS: All the studies included were designed for patient home-based care application and provided a mechanism to communicate with caregivers. A targeted study population such as older patients should be considered to maximize the public health impact on the self-management of diseases. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42018096627; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=96627.

TNF-α blockers for the treatment of Kawasaki disease in children.

BACKGROUND: Kawasaki disease (KD) is an acute inflammatory vasculitis (inflammation of the blood vessels) that mainly affects children between six months and five years of age. The vasculitis primarily impacts medium-sized blood vessels, especially in the coronary arteries. In most children, intravenous immunoglobulin (IVIG) and aspirin therapy rapidly reduce inflammatory markers, fever, and other clinical symptoms. However, approximately 15% to 20% of children receiving the initial IVIG infusion show persistent or recurrent fever and are classified as IVIG-resistant. Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that plays an important role in host defence against infections and in immune responses. Several studies have established that blocking TNF-α is critical for obtaining anti-inflammatory effects in children with KD, thus, there is a need to identify benefits and risks of TNF-α blockers for the treatment of KD. OBJECTIVES: To evaluate the efficacy and safety of using TNF-α blockers (i.e. infliximab and etanercept) to treat children with Kawasaki disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 19 September 2018. We also undertook reference checking of grey literature. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared TNF-α blockers (i.e. infliximab and etanercept) to placebo or other drugs (including retreatment with IVIG) in children with KD, reported in abstract or full-text. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the study selection criteria, assessed risk of bias and extracted data. When necessary, we contacted study authors for additional information. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included five trials from 14 reports, with a total of 494 participants. All included trials were individual RCTs that examined the effect of TNF-α blockers for KD.Five trials (with 494 participants) reported the incidence of treatment resistance. TNF-α blockers reduced the incidence of treatment resistance (TNF-α blocker intervention group 30/237, control group 58/257; risk ratio (RR) 0.57, 95% confidence interval (CI) 0.38 to 0.86; low-certainty evidence).Four trials reported the incidence of coronary artery abnormalities (CAAs). Three trials (with 270 participants) contributed data to the meta-analysis, since we could not get the data needed for the analysis from the fourth trial. There was no clear difference between groups in the incidence of CAAs (TNF-α blocker intervention group 8/125, control group 9/145; RR 1.18, 95% CI 0.45 to 3.12; low-certainty evidence).Three trials with 250 participants reported the adverse effect 'infusion reactions' after treatment initiation. The TNF-α blocker intervention decreased infusion reactions (TNF-α blocker intervention group 0/126, control group 15/124; RR 0.06, 95% CI 0.01 to 0.45; low-certainty evidence).Two trials with 227 participants reported the adverse effect 'infections' after treatment initiation. There was no clear difference between groups (TNF-α blocker intervention group 7/114, control group 10/113; RR 0.68, 95% CI 0.33 to 1.37; low-certainty evidence).One trial (with 31 participants) reported the adverse effect 'cutaneous reactions' (rash and contact dermatitis). There was no clear difference between the groups for incidence of rash (TNF-α blocker intervention group 2/16, control group 0/15; RR 4.71, 95% CI 0.24 to 90.69; very low-certainty evidence) or for incidence of contact dermatitis (TNF-α blocker intervention group 1/16, control group 3/15; RR 0.31, 95% CI 0.04 to 2.68; very low-certainty evidence).No trials reported other adverse effects such as injection site reactions, neutropenia, infections, demyelinating disease, heart failure, malignancy, and induction of autoimmunity. AUTHORS' CONCLUSIONS: We found a limited number of RCTs examining the effect of TNF-α blockers for KD. In summary, low-certainty evidence indicates that TNF-α blockers have beneficial effects on treatment resistance and the adverse effect 'infusion reaction' after treatment initiation for KD when compared with no treatment or additional treatment with IVIG. Further research will add to the evidence base. Due to the small number of underpowered trials contributing to the analyses, the results presented should be treated with caution. Further large high quality trials with timing and type of TNF-α blockers used are needed to determine the effects of TNF-α blockers for KD.

Skin preparation for preventing infection following caesarean section.

BACKGROUND: The risk of maternal mortality and morbidity (particularly postoperative infection) is higher for caesarean section (CS) than for vaginal birth. With the increasing rate of CS, it is important to minimise the risks to the mother as much as possible. This review focused on different forms and methods of preoperative skin preparation to prevent infection. This review is an update of a review that was first published in 2012, and updated in 2014. OBJECTIVES: To compare the effects of different antiseptic agents, different methods of application, or different forms of antiseptic used for preoperative skin preparation for preventing postcaesarean infection. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (27 November 2017), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised trials, evaluating any type of preoperative skin preparation agents, forms, and methods of application for caesarean section.Comparisons of interest in this review were between different antiseptic agents used for CS skin preparation (e.g. alcohol, povidone iodine), different methods of antiseptic application (e.g. scrub, paint, drape), different forms of antiseptic (e.g. powder, liquid), and also between different skin preparations, such as a plastic incisional drape, which may or may not be impregnated with antiseptic agents.Only studies involving the preparation of the incision area were included. This review did not cover studies of preoperative handwashing by the surgical team or preoperative bathing. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed all potential studies for inclusion, assessed risk of bias, and extracted the data using a predesigned form. We checked data for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: For this update, we included 11 randomised controlled trials (RCTs), with a total of 6237 women who were undergoing CS. Ten trials (6215 women) contributed data to this review. All included studies were individual RCTs. We did not identify any quasi- or cluster-RCTs. The trial dates ranged from 1983 to 2016. Six trials were conducted in the USA, and the remainder in Nigeria, South Africa, France, Denmark, and Indonesia.The included studies were broadly methodologically sound, but raised some specific concerns regarding risk of bias in a number of cases.Drape versus no drapeThis comparison investigated the use of a non-impregnated drape versus no drape, following preparation of the skin with antiseptics. For women undergoing CS, low-quality evidence suggested that using a drape before surgery compared with no drape, may make little or no difference to the incidence of surgical site infection (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.97 to 1.71; 2 trials, 1294 women), or length of stay in the hospital (mean difference (MD) 0.10 day, 95% CI -0.27 to 0.46 1 trial, 603 women).One-minute alcohol scrub with iodophor drape versus five-minute iodophor scrub without drapeOne trial compared an alcohol scrub and iodophor drape with a five-minute iodophor scrub only, and reported no surgical site infection in either group (79 women, very-low quality evidence). We were uncertain whether the combination of a one-minute alcohol scrub and a drape reduced the incidence of endomyometritis when compared with a five-minute scrub, because the quality of the evidence was very low (RR 1.62, 95% CI 0.29 to 9.16; 1 trial, 79 women).Parachlorometaxylenol with iodine versus iodine aloneWe were uncertain whether parachlorometaxylenol with iodine before CS made any difference to the incidence of surgical site infection (RR 0.33, 95% CI 0.04 to 2.99; 1 trial, 50 women), or endometritis (RR 0.88, 95% CI 0.56 to 1.38; 1 trial, 50 women) when compared with iodine alone, because the quality of the evidence was very low.Chlorhexidine gluconate versus povidone iodineLow-quality evidence suggested that chlorhexidine gluconate before CS, when compared with povidone iodine, may make little or no difference to the incidence of surgical site infection (RR 0.80, 95% CI 0.62 to 1.02; 6 trials, 3607 women). However, surgical site infection appeared to be slightly reduced for women for whom chlorhexidine gluconate was used compared with povidone iodine after we removed four trials at high risk of bias for outcome assessment, in a sensitivity analysis (RR 0.59, 95% CI 0.37 to 0.95; 2 trials, 1321 women).Low-quality evidence indicated that chlorhexidine gluconate before CS, when compared with povidone iodine, may make little or no difference to the incidence of endometritis (RR 1.01, 95% CI 0.51 to 2.01; 2 trials, 2079 women), or to reducing maternal skin irritation or allergic skin reaction (RR 0.60, 95% CI 0.22 to 1.63; 2 trials, 1521 women).One small study (60 women) reported reduced bacterial growth at 18 hours after CS for women who had chlorhexidine gluconate preparation compared with women who had povidone iodine preparation (RR 0.23, 95% CI 0.07 to 0.70).None of the included trials reported on maternal mortality or repeat surgery.Chlorhexidine 0.5% versus 70% alcohol plus drapeOne trial, which was only available as an abstract, investigated the effect of skin preparation on neonatal adverse events, and found cord blood iodine concentration to be higher in the iodine group. AUTHORS' CONCLUSIONS: There was insufficient evidence available from the included RCTs to fully evaluate different agents and methods of skin preparation for preventing infection following caesarean section. Therefore, it is not yet clear what sort of skin preparation may be most effective for preventing postcaesarean surgical site infection, or for reducing other undesirable outcomes for mother and baby.Most of the evidence in this review was deemed to be very low or low quality. This means that for most findings, our confidence in any evidence of an intervention effect is limited, and indicates the need for more high-quality research.This field needs high quality, well designed RCTs, with larger sample sizes. High priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), and application methods (scrubbing, swabbing, or draping). We found four studies that were ongoing; we will incorporate the results of these studies in future updates of this review.

Bed rest with and without hospitalisation in multiple pregnancy for improving perinatal outcomes.

BACKGROUND: Strict or partial bed rest in hospital or at home is commonly recommended for women with multiple pregnancy to improve pregnancy outcomes. In order to advise women to rest in bed for any length of time, a policy for clinical practice needs to be supported by reliable evidence and weighed against possible adverse effects resulting from prolonged activity restriction. OBJECTIVES: The objective of this review is to assess the effectiveness of bed rest in hospital or at home to improve perinatal outcomes in women with a multiple pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 May 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (30 May 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We selected all individual and cluster-randomised controlled trials evaluating the effect of strict or partial bed rest at home or in hospital compared with no activity restriction during multiple pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data and methodological quality. We evaluated the quality of the evidence using the GRADE approach and summarised it in 'Summary of findings' tables. MAIN RESULTS: We included six trials, involving a total of 636 women with a twin or triplet pregnancy (total of 1298 babies). We assessed all of the included trials as having a low risk of bias for random sequence generation. Apart from one trial with an unclear risk of bias, we judged all remaining trials to be of low risk of bias for allocation concealment.Five trials (495 women and 1016 babies) compared strict bed rest in hospital with no activity restriction at home. There was no difference in the risk of very preterm birth (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.66 to 1.58, five trials, 495 women, assuming complete correlation between twins/triplets, low-quality evidence), perinatal mortality (RR 0.65, 95% CI 0.35 to 1.21, five trials, 1016 neonates, assuming independence between twins/triplets, low-quality evidence) and low birthweight (RR 0.95, 95% CI 0.75 to 1.21, three trials, 502 neonates, assuming independence between twins/triplets, low-quality evidence). We observed no differences for the risk of small-for-gestational age (SGA) (RR 0.75, 95% CI 0.56 to 1.01, two trials, 293 women, assuming independence between twins/triplets, low-quality evidence) and prelabour preterm rupture of the membrane (PPROM) (RR 1.30, 95% CI 0.71 to 2.38, three trials, 276 women, low-quality evidence). However, strict bed rest in hospital was associated with increased spontaneous onset of labour (RR 1.05, 95% CI 1.02 to 1.09, P = 0.004, four trials, 488 women) and a higher mean birthweight (mean difference (MD) 136.99 g, 95% CI 39.92 to 234.06, P = 0.006, three trials, 314 women) compared with no activity restriction at home.Only one trial (141 women and 282 babies) compared partial bed rest in hospital with no activity restriction at home. There was no evidence of a difference in the incidence of very preterm birth (RR 2.30, 95% CI 0.84 to 6.27, 141 women, assuming complete correlation between twins, low-quality evidence) and perinatal mortality (RR 4.17, 95% CI 0.90 to 19.31, 282 neonates, assuming complete independence twins, low-quality evidence) between the intervention and control group. Low birthweight was not reported in this trial. We found no differences in the risk of PPROM and SGA between women receiving partial bed rest and the control group (low-quality evidence). Women on partial bed rest in hospital were less likely to develop gestational hypertension compared with women without activity restriction at home (RR 0.30, 95% CI 0.16 to 0.59, P = 0.0004, 141 women).Strict or partial bed rest in hospital was found to have no impact on other secondary outcomes. None of the trials reported on costs of the intervention or adverse effects such as the development of venous thromboembolism or psychosocial effects. AUTHORS' CONCLUSIONS: The evidence to date is insufficient to inform a policy of routine bed rest in hospital or at home for women with a multiple pregnancy. There is a need for large-scale, multicenter randomised controlled trials to evaluate the benefits, adverse effects and costs of bed rest before definitive conclusions can be drawn.

Vitamin supplementation for preventing miscarriage.

BACKGROUND: Miscarriage is a common complication of pregnancy that can be caused by a wide range of factors. Poor dietary intake of vitamins has been associated with an increased risk of miscarriage, therefore supplementing women with vitamins either prior to or in early pregnancy may help prevent miscarriage. OBJECTIVES: The objectives of this review were to determine the effectiveness and safety of any vitamin supplementation, on the risk of spontaneous miscarriage. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (6 November 2015) and reference lists of retrieved studies. SELECTION CRITERIA: All randomised and quasi-randomised trials comparing supplementation during pregnancy with one or more vitamins with either placebo, other vitamins, no vitamins or other interventions. We have included supplementation that started prior to conception, periconceptionally or in early pregnancy (less than 20 weeks' gestation). DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion, extracted data and assessed trial quality. We assessed the quality of the evidence using the GRADE approach. The quality of evidence is included for numerical results of outcomes included in the 'Summary of findings' tables. MAIN RESULTS: We included a total of 40 trials (involving 276,820 women and 278,413 pregnancies) assessing supplementation with any vitamin(s) starting prior to 20 weeks' gestation and reporting at least one primary outcome that was eligible for the review. Eight trials were cluster-randomised and contributed data for 217,726 women and 219,267 pregnancies in total.Approximately half of the included trials were assessed to have a low risk of bias for both random sequence generation and adequate concealment of participants to treatment and control groups. Vitamin C supplementation There was no difference in the risk of total fetal loss (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.92 to 1.40, seven trials, 18,949 women; high-quality evidence); early or late miscarriage (RR 0.90, 95% CI 0.65 to 1.26, four trials, 13,346 women; moderate-quality evidence); stillbirth (RR 1.31, 95% CI 0.97 to 1.76, seven trials, 21,442 women; moderate-quality evidence) or adverse effects of vitamin supplementation (RR 1.16, 95% CI 0.39 to 3.41, one trial, 739 women; moderate-quality evidence) between women receiving vitamin C with vitamin E compared with placebo or no vitamin C groups. No clear differences were seen in the risk of total fetal loss or miscarriage between women receiving any other combination of vitamin C compared with placebo or no vitamin C groups. Vitamin A supplementation No difference was found in the risk of total fetal loss (RR 1.01, 95% CI 0.61 to 1.66, three trials, 1640 women; low-quality evidence); early or late miscarriage (RR 0.86, 95% CI 0.46 to 1.62, two trials, 1397 women; low-quality evidence) or stillbirth (RR 1.29, 95% CI 0.57 to 2.91, three trials, 1640 women; low-quality evidence) between women receiving vitamin A plus iron and folate compared with placebo or no vitamin A groups. There was no evidence of differences in the risk of total fetal loss or miscarriage between women receiving any other combination of vitamin A compared with placebo or no vitamin A groups. Multivitamin supplementation There was evidence of a decrease in the risk for stillbirth among women receiving multivitamins plus iron and folic acid compared iron and folate only groups (RR 0.92, 95% CI 0.85 to 0.99, 10 trials, 79,851 women; high-quality evidence). Although total fetal loss was lower in women who were given multivitamins without folic acid (RR 0.49, 95% CI 0.34 to 0.70, one trial, 907 women); and multivitamins with or without vitamin A (RR 0.60, 95% CI 0.39 to 0.92, one trial, 1074 women), these findings included one trial each with small numbers of women involved. Also, they include studies where the comparison groups included women receiving either vitamin A or placebo, and thus require caution in interpretation.We found no difference in the risk of total fetal loss (RR 0.96, 95% CI 0.93 to 1.00, 10 trials, 94,948 women; high-quality evidence) or early or late miscarriage (RR 0.98, 95% CI 0.94 to 1.03, 10 trials, 94,948 women; moderate-quality evidence) between women receiving multivitamins plus iron and folic acid compared with iron and folate only groups.There was no evidence of differences in the risk of total fetal loss or miscarriage between women receiving any other combination of multivitamins compared with placebo, folic acid or vitamin A groups. Folic acid supplementation There was no evidence of any difference in the risk of total fetal loss, early or late miscarriage, stillbirth or congenital malformations between women supplemented with folic acid with or without multivitamins and/or iron compared with no folic acid groups. Antioxidant vitamins supplementation There was no evidence of differences in early or late miscarriage between women given antioxidant compared with the low antioxidant group (RR 1.12, 95% CI 0.24 to 5.29, one trial, 110 women). AUTHORS' CONCLUSIONS: Taking any vitamin supplements prior to pregnancy or in early pregnancy does not prevent women experiencing miscarriage. However, evidence showed that women receiving multivitamins plus iron and folic acid had reduced risk for stillbirth. There is insufficient evidence to examine the effects of different combinations of vitamins on miscarriage and miscarriage-related outcomes.

The efficacy and safety of anamorelin for patients with cancer-related anorexia/cachexia syndrome: a systematic review and meta-analysis.

Cancer-related anorexia/cachexia syndrome (CACS) is characterized by anorexia and loss of body weight. Evidence is insufficient to strongly endorse any pharmacologic agent for the treatment of CACS. In this systematic review, we assessed the efficacy of oral anamorelin treatment for patients with CACS. On July 6, 2022, we systematically searched the following databases for randomized controlled trials (RCTs) of adults with CACS comparing oral anamorelin versus placebo: CENTRAL, PubMed, EMBASE, and ICHUSHI. The primary outcomes were total body weight (TBW), patient-reported quality of life (QOL), and adverse events (AEs). Secondary outcomes included lean body mass (LBM), overall survival (OS), non-dominant hand grip strength (HGS), and appetite. We included seven RCTs with a total of 1944 CACS patients. Anamorelin significantly increased TBW (mean difference (MD) 1.73, 95% confidence interval (CI) 1.34-2.13, p < 0.00001), LBM (MD 1.06, 95% CI 0.30-1.81, p = 0.006), and QOL (standardized mean difference (SMD) 0.16, 95% CI 0.04-0.27, p = 0.006) compared with placebo without a significant difference in all AEs, severe AEs, OS, HGS or appetite. Anamorelin may be an effective treatment for CACS patients; however, further studies are needed to confirm the efficacy and safety of this drug.

The Current Concept of Paternal Bonding: A Systematic Scoping Review.

Bonding is crucial to perinatal mental health. Despite an extensive body of literature on maternal bonding, few studies have focused on paternal bonding. This scoping review aimed to clarify the current state of the concept of paternal-infant/fetus bonding. The eligibility criteria were drawn from the population concept and context elements to answer the following questions: "what is paternal bonding?" and "what are the constructs of the concept of paternal bonding?" The review comprised 39 studies. Paternal bonding was associated with both positive and negative paternal behavior and thought and may be determined based on fathers' beliefs and rearing history. Most studies showed that father-child interaction is one of the factors promoting paternal bonding. However, fathers generally felt more distant from their babies post-delivery than mothers. Only a few studies originally defined paternal bonding; most relied on the definitions of maternal bonding. We found different descriptions lacking consensus. Few studies examined the differences between paternal and maternal bonding. No consensus exists on the concept, constructs, and assessment of paternal bonding. The causal relationship between paternal bonding and other variables is unexplored. Future studies should explore fathers' perspectives and experiences, focusing on the unknown aspects of paternal bonding identified in this review.

Polymorphisms Contributing to Calcium Status: A Systematic Review.

This systematic review assessed genotypes and changes in calcium homeostasis. A literature search was performed in EMBASE, Medline and CENTRAL on 7 August 2020 identifying 1012 references. Studies were included with any human population related to the topic of interest, and genetic variations in genes related to calcium metabolism were considered. Two reviewers independently screened references, extracted relevant data and assessed study quality using the Q-Genie tool. Forty-one studies investigating Single Nucleotide Polymorphisms (SNPs) in relation to calcium status were identified. Almost half of the included studies were of good study quality according to the Q-Genie tool. Seventeen studies were cross-sectional, 14 case-control, seven association and three were Mendelian randomization studies. Included studies were conducted in over 18 countries. Participants were mainly adults, while six studies included children and adolescents. Ethnicity was described in 31 studies and half of these included Caucasian participants. Twenty-six independent studies examined the association between calcium and polymorphism in the calcium-sensing receptor (CASR) gene. Five studies assessed the association between polymorphisms of the Vitamin D receptor (VDR) gene and changes in calcium levels or renal excretion. The remaining ten studies investigated calcium homeostasis and other gene polymorphisms such as the CYP24A1 SNP or CLDN14. This study identified several CASR, VDR and other gene SNPs associated with calcium status. However, to provide evidence to guide dietary recommendations, further research is needed to explore the association between common polymorphisms and calcium requirements.

Health Facility Staff Training for Improving Breastfeeding Outcome: A Systematic Review for Step 2 of the Baby-Friendly Hospital Initiative.

The Baby-Friendly Hospital Initiative (BFHI) implemented through the "Ten Steps to Successful Breastfeeding" has been widely promoted as an intervention that improves breastfeeding rates. Step 2 requires the training of all healthcare staff in skills that are necessary to implement the policy. This systematic review provides evidence about the effect of training healthcare staff in hospitals and birth centers on breastfeeding outcomes. Randomized controlled trials (RCT), quasi-RCT, and controlled before and after (CBA) studies comparing training of healthcare staff on breastfeeding and supportive feeding practices with no training were included in this review. We searched CENTRAL PubMed, EMBASE, CINAHL, Web of Science, and the British Nursing Index for studies. Studies were screened against predetermined criteria, and risk of bias of included studies was assessed using the Risk of Bias Assessment tool for Non-Randomized Studies for non-RCT studies and the Cochrane Handbook for Systematic Reviews of Interventions for RCT studies. Of the six studies included in this review, three were RCT whereas three were CBA studies. The studies were conducted in 5 countries and involved 390 healthcare staff. Provision of educational interventions aimed at increasing knowledge and practice of BFHI and support was found to improve health worker's knowledge, attitude, and compliance with the BFHI practices. In one study, the rate of exclusive breastfeeding increased at the intervention site but no differences were found for breastfeeding initiation rates. All included studies had methodological limitations, and study designs and methodologies lacked comparability.

Effects of nutrition interventions during pregnancy on low birth weight: an overview of systematic reviews.

INTRODUCTION: Low birth weight (LBW, birth weight less than 2500 g) is associated with infant mortality and childhood morbidity. Poor maternal nutritional status is one of several contributing factors to LBW. We systematically reviewed the evidence for nutrition-specific (addressing the immediate determinants of nutrition) and nutrition-sensitive (addressing the underlying cause of undernutrition) interventions to reduce the risk of LBW and/or its components: preterm birth (PTB) and small-for-gestational age (SGA). METHODS: We conducted a comprehensive literature search in MEDLINE, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews (September 2015). Systematic reviews of randomised controlled trials focusing on nutritional interventions before and during pregnancy to reduce LBW and its components were eligible for inclusion into the overview review. We assessed the methodological quality of the included reviews using A Measurement Tool to Assess Reviews (AMSTAR), PROSPERO: CRD42015024814. RESULTS: We included 23 systematic reviews which comprised 34 comparisons. Sixteen reviews were of high methodological quality, six of moderate and only one review of low quality. Six interventions were associated with a decreased risk of LBW: oral supplementation with (1) vitamin A, (2) low-dose calcium, (3) zinc, (4) multiple micronutrients (MMN), nutritional education and provision of preventive antimalarials. MMN and balanced protein/energy supplementation had a positive effect on SGA, while high protein supplementation increased the risk of SGA. High-dose calcium, zinc or long-chain n-3 fatty acid supplementation and nutritional education decreased the risk of PTB. CONCLUSION: Improving women's nutritional status positively affected LBW, SGA and PTB. Based on current evidence, especially MMN supplementation and preventive antimalarial drugs during pregnancy may be considered for policy and practice. However, for most interventions evidence was derived from a small number of trials and/or participants. There is a need to further explore the evidence of nutrition-specific and nutrition-sensitive interventions in order to reach the WHO's goal of a 30% reduction in the global rate of LBW by 2025.

Titin visualization in real time reveals an unexpected level of mobility within and between sarcomeres.

The giant muscle protein titin is an essential structural component of the sarcomere. It forms a continuous periodic backbone along the myofiber that provides resistance to mechanical strain. Thus, the titin filament has been regarded as a blueprint for sarcomere assembly and a prerequisite for stability. Here, a novel titin-eGFP knockin mouse provided evidence that sarcomeric titin is more dynamic than previously suggested. To study the mobility of titin in embryonic and neonatal cardiomyocytes, we used fluorescence recovery after photobleaching and investigated the contribution of protein synthesis, contractility, and calcium load to titin motility. Overall, the kinetics of lateral and longitudinal movement of titin-eGFP were similar. Whereas protein synthesis and developmental stage did not alter titin dynamics, there was a strong, inhibitory effect of calcium on titin mobility. Our results suggest a model in which the largely unrestricted movement of titin within and between sarcomeres primarily depends on calcium, suggesting that fortification of the titin filament system is activity dependent.