Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization.

BACKGROUND: Immobilization of the lower limb is a risk factor for venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are anticoagulants, which might be used in adult patients with lower-limb immobilization to prevent deep venous thrombosis (DVT) and its complications. This is an update of the review first published in 2008. OBJECTIVES: To assess the effectiveness of low molecular weight heparin for the prevention of venous thromboembolism in patients with lower-limb immobilization in an ambulatory setting. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Specialised Register, CENTRAL, and three trials registers (April 2017). SELECTION CRITERIA: Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-limb immobilization. Immobilization was by means of a plaster cast or brace. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager 5. MAIN RESULTS: We included eight RCTs that fulfilled our criteria, with a total of 3680 participants. The quality of evidence, according GRADE, varied by outcome and ranged from low to moderate. We found an incidence of DVT ranging from 4.3% to 40% in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week, and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization, with event rates ranging from 0% to 37% (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33 to 0.61; with minimal evidence of heterogeneity: I² = 26%, P = 0.23; seven studies; 1676 participants, moderate-quality evidence). Comparable results were seen in the following groups of participants: patients with below-knee casts, conservatively treated patients (non-operated patients), operated patients, patients with fractures, patients with soft-tissue injuries, and patients with distal or proximal thrombosis. No clear differences were found between the LMWH and control groups for pulmonary embolism (OR 0.50, 95% CI 0.17 to 1.47; with no evidence of heterogeneity: I² = 0%, P = 0.56; five studies, 2517 participants; low-quality evidence). The studies also showed less symptomatic VTE in the LMWH groups compared with the control groups (OR 0.40, 95% CI 0.21 to 0.76; with minimal evidence of heterogeneity: I² = 16%, P = 0.31; six studies; 2924 participants; low-quality evidence). One death was reported in the included studies, but no deaths due to pulmonary embolism were reported. Complications of major adverse events were rare, with minor bleeding the main adverse events reported. AUTHORS' CONCLUSIONS: Moderate-quality evidence showed that the use of LMWH in outpatients reduced DVT when immobilization of the lower limb was required, when compared with no prophylaxis or placebo. The quality of the evidence was reduced to moderate because of risk of selection and attrition bias in the included studies. Low-quality evidence showed no clear differences in PE between the LMWH and control groups, but less symptomatic VTE in the LMWH groups. The quality of the evidence was downgraded due to risk of bias and imprecision.

High variability and low irradiance of phototherapy devices in Dutch NICUs.

OBJECTIVE: To evaluate phototherapy practices by measuring the irradiance levels of phototherapy (PT) devices. DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care units. PATIENTS: None. INTERVENTIONS: Irradiance levels of PT devices used in the 10 Dutch Neonatal Intensive Care Units (NICUs) were measured according to the local PT practice patterns. The irradiance levels of all overhead and fibre-optic PT devices were measured with a radiometer using an infant silhouette model. RESULTS: Eight different PT devices were used in the 10 NICUs; five were overhead devices and three fibre-optic pads. The median (range) irradiance level for overhead PT devices was 9.7 (4.3-32.6) µW/cm(2)/nm and for fibre-optic pads 6.8 (0.8-15.6) µW/cm(2)/nm. Approximately 50% of PT devices failed to meet the minimal recommended irradiance level of 10 µW/cm(2)/nm. Maximal irradiance levels for overhead PT spot lights were inversely related to the distance between device and infant model (R2=0.33). The distances ranged from 37 cm to 65 cm. CONCLUSIONS: PT devices in the Dutch NICUs show considerable variability with often too low irradiance levels. These results indicate that suboptimal PT is frequently applied and may even be ineffective towards reducing total serum bilirubin levels. These results underline the need for greater awareness among all healthcare workers towards the requirements for effective PT including measurements of irradiance and distance.

Morphologic abnormalities in 2-year-old children born after in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic screening: follow-up of a randomized controlled trial.

OBJECTIVE: To evaluate the effect of preimplantation genetic screening (PGS) on morphologic outcome in children. DESIGN: Follow-up of a randomized controlled trial (RCT). SETTING: University hospital. PATIENT(S): Two-year-old children born to mothers who participated in an RCT on the efficacy of PGS: 50 children born after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with PGS (intervention group; PGS+) and 72 children born after IVF/ICSI only (control group; PGS-). Sixty-six age-matched children conceived without any form of assisted reproduction were recruited separately in a local public health service center (reference group). INTERVENTION(S): PGS. MAIN OUTCOME MEASURE(S): Body surface examination and anthropometry. The evaluation of morphologic abnormalities allowed assessment of children's phenotype in detail. Morphologic abnormalities were classified as major abnormalities (abnormal development in organogenesis, deformations, disruptions, or dysplasia) and minor anomalies (deviations in phenogenesis). RESULT(S): The percentage of children with ≥ 1 major abnormality was 28% in the PGS+ and 35% in the PGS- group [difference -7%, 95% CI -23% to 10%]. The percentage of children with ≥ 1 minor anomaly was 64% in the PGS+ and 67% in the PGS- group [difference -3%, 95% CI -15% to 20%]. In the reference group 30% of the children had ≥ 1 major abnormality [95% CI 20% to 43%] and 74% had ≥ 1 minor anomaly [95% CI 62% to 84%]. CONCLUSION(S): No statistically significant differences were found in minor anomalies between children conceived after IVF/ICSI with or without PGS. There is < 2.5% chance of ≥ 10% more major abnormalities in children born after PGS.

Mental, psychomotor, neurologic, and behavioral outcomes of 2-year-old children born after preimplantation genetic screening: follow-up of a randomized controlled trial.

OBJECTIVE: To evaluate the effect of preimplantation genetic screening (PGS) on neurodevelopmental outcomes in children. DESIGN: Prospective, assessor-blinded, follow-up study of children born to women randomly assigned to in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) with or without PGS. SETTING: University Medical Center, Groningen, and Academic Medical Center, Amsterdam, the Netherlands. PATIENT(S): Fifty-four PGS children and 77 controls. INTERVENTION(S): PGS. MAIN OUTCOME MEASURE(S): Mental, psychomotor, neurologic, and behavioral outcomes in 2-year-old children as measured with the Bayley Scales of Infant Development, the Hempel neurologic examination, and the Child Behavior Check List. RESULT(S): The mental, psychomotor, and behavioral outcomes at 2 years in children born after IVF with and without PGS were similar overall. The PGS children showed lower neurologic optimality scores than the control children. Scores on all tests were within the normal range. CONCLUSION(S): Conception with PGS does not seem to be associated with impaired mental, psychomotor, or behavioral outcomes by age 2. However, the lower neurologic optimality scores found in the PGS children may signal less favorable long-term neurologic outcomes in PGS children. Our findings stress the need for safety evaluations with new assisted reproductive techniques before large-scale implementation.

Assessment of neonatal resuscitation skills: a reliable and valid scoring system.

OBJECTIVE: To study the reliability and validity of a scoring instrument for the assessment of neonatal resuscitation skills in a training setting. METHODS: Fourteen paediatric residents performed a neonatal resuscitation on a manikin, while being recorded with a video camera. The videotapes were analysed using an existing scoring instrument with an established face and content validity, adjusted for use in a training setting. Intra- and inter-rater reliability were assessed by comparing the ratings of the videotapes of three raters, one of who rated the videotapes twice. Intra-class coefficients (ICC) were calculated for the sum score, percentages of agreement and kappa coefficients for the individual items. To study construct validity, the performance of a second resuscitation of by residents was assessed after they had received feedback on their first performance. RESULTS: The ICC were 0.95 and 0.77 for intra- and inter-rater reliability, respectively. The median percentage of intra-rater agreement was 100%; inter-rater agreement 78.6-84.0%. The median kappa was 0.85 for intra-rater reliability, and 0.42-0.59 for inter-rater reliability. Residents showed a 10% improvement (95% confidence interval -4; 23%) on performance of a second resuscitation, which supports the instrument's construct validity. CONCLUSION: A useful and valid instrument with good intra-rater and reasonable inter-rater reliability is now available for the assessment of neonatal resuscitation skills in a training setting. Its reliability can be improved by using a more advanced manikin and by training of the raters.