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Objective: Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years. Design: A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers. Subjects: A total of 564 adults ( n =90–98 per group; body mass index 30–40 kg m −2 ) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n =90–95), placebo ( n =98) or open-label orlistat (120 mg × 3, n =95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007–April 2009 and is registered with Clinicaltrials.gov , number NCT00480909. Results: From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7–8.0) more weight than those on placebo and 3.8 kg (1.6–6.0) more than those on orlistat ( P ⩽0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n =184) lost 3.0 kg (1.3–4.7) more weight than those on orlistat ( n =95; P <0.001). Completers on liraglutide 2.4/3.0 mg ( n =92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids. Conclusion: Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.

ObjectiveTo determine the association between SpO2 at 5 min and preterm infant outcomes.DesignData from 768 infants <32 weeks gestation from 8 randomised controlled trials (RCTs) of lower (≤0.3) versus higher (≥0.6) initial inspiratory fractions of oxygen (FiO2) for resuscitation, were examined.SettingIndividual patient analysis of 8 RCTsInterventionsLower (≤0.3) versus higher (≥0.6) oxygen resuscitation strategies targeted to specific predefined SpO2 before 10 min of age.PatientsInfants <32 weeks gestation.Main outcome measuresRelationship between SpO2 at 5 min, death and intraventricular haemorrhage (IVH) >grade 3.Results5 min SpO2 data were obtained from 706 (92%) infants. Only 159 (23%) infants met SpO2 study targets and 323 (46%) did not reach SpO280%. Pooled data showed decreased likelihood of reaching SpO280% if resuscitation was initiated with FiO2 <0.3 (OR 2.63, 95% CI 1.21 to 5.74, p<0.05). SpO2 <80% was associated with lower heart rates (mean difference −8.37, 95% CI −15.73 to –1.01, *p<0.05) and after accounting for confounders, with IVH (OR 2.04, 95% CI 1.01 to 4.11, p<0.05). Bradycardia (heart rate <100 bpm) at 5 min increased risk of death (OR 4.57, 95% CI 1.62 to 13.98, p<0.05). Taking into account confounders including gestation, birth weight and 5 min bradycardia, risk of death was significantly increased with time taken to reach SpO280%.ConclusionNot reaching SpO280% at 5 min is associated with adverse outcomes, including IVH. Whether this is because of infant illness or the amount of oxygen that is administered during stabilisation is uncertain and needs to be examined in randomised trials

Background: Liraglutide 3.0 mg, with diet and exercise, produced substantial weight loss over 1 year that was sustained over 2 years in obese non-diabetic adults. Nausea was the most frequent side effect. Objective: To evaluate routinely collected data on nausea and vomiting among individuals on liraglutide and their influence on tolerability and body weight. Design: A randomized, placebo-controlled, double-blind 20-week study with an 84-week extension (sponsor unblinded at 20 weeks, open-label after 1 year) in eight European countries (Clinicaltrials.gov: NCT00422058). Subjects: After commencing a 500-kcal/day deficit diet plus exercise, 564 participants (18–65 years, body mass index (BMI) 30–40 kg m −2 ) were randomly assigned (after a 2-week run-in period) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg), placebo or open-label orlistat (120 mg × 3 per day). After 1 year, participants on liraglutide/placebo switched to liraglutide 2.4 mg, and subsequently, to liraglutide 3.0 mg (based on 20-week and 1-year results, respectively). Results: The intention-to-treat population comprised 561 participants ( n= 90–98 per arm, age 45.9±10.3 years, BMI 34.8±2.7 kg m −2 (mean±s.d.)). In year 1, more participants reported ⩾1 episode of nausea/vomiting on treatment with liraglutide 1.2–3.0 mg (17–38%) than with placebo or orlistat (both 4%, P ⩽0.001). Most episodes occurred during dose escalation (weeks 1–6), with ‘mild’ or ‘moderate’ symptoms. Among participants on liraglutide 3.0 mg, 48% reported some nausea and 13% some vomiting, with considerable variation between countries, but only 4 out of 93 (4%) reported withdrawals. The mean 1-year weight loss on treatment with liraglutide 3.0 mg from randomization was 9.2 kg for participants reporting nausea/vomiting episodes, versus 6.3 kg for those with none (a treatment difference of 2.9 kg (95% confidence interval 0.5–5.3); P =0.02). Both weight losses were significantly greater than the respective weight losses for participants on placebo ( P <0.001) or orlistat ( P <0.05). Quality-of-life scores at 20 weeks improved similarly with or without nausea/vomiting on treatment with liraglutide 3.0 mg. Conclusion: Transient nausea and vomiting on treatment with liraglutide 3.0 mg was associated with greater weight loss, although symptoms appeared tolerable and did not attenuate quality-of-life improvements. Improved data collection methods on nausea are warranted.

In this clinical trial, the appetite suppressant sibutramine as compared with placebo resulted in modest weight loss but also in an unexpected increase in the risk of nonfatal myocardial infarction and stroke (a finding limited to patients with preexisting cardiovascular disease). Sibutramine should not be used in patients with cardiovascular disease. Obesity and excess weight are escalating public health concerns because they increase the prevalence of associated conditions such as diabetes mellitus and the risk of premature death. 1 , 2 More than 80% of even highly motivated patients are unable to achieve weight loss with dietary and lifestyle modifications alone. 3 Sibutramine is a norepinephrine and serotonin reuptake inhibitor that was approved for weight management in patients who are unable to lose weight by means of diet and exercise alone. Sibutramine induces satiety (resulting in reduced food intake) and an increase in energy expenditure. 4 , 5 In some patients, sibutramine increases blood pressure, pulse . . .

Background Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85–95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO 2 ) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3–0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. Methods An international cluster, cross-over randomized trial of initial FiO 2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 23 0/7 and 28 6/7  weeks’ gestation will be eligible. Each participating hospital will be randomized to either an initial FiO 2 concentration of either 0.3 or 0.6 to recruit for up to 12 months’ and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO 2 of 0.6, and the comparator will be initial FiO 2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). Discussion The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18–24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. Trial registration The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia. Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age. Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability. Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy.

Objective: Delivery room management interventions have been successfully implemented via collaborative quality improvement (QI) projects. However, it is unknown whether these successes translate to reductions in neonatal morbidity and mortality. Study Design: This was a prospective pre–post intervention study of three nonrandomized hospital groups within the California Perinatal Quality Care Collaborative. A collaborative QI model (Collaborative QI) was compared with a single-site QI model (NICU QI) and a non-participant population when implementing evidence-based delivery room practices. The intervention period was between June 2011 and May 2012. Infants born with gestational age between 22 weeks 0 days and 29 weeks 6 days and birth weight ⩽1500 g were included. Outcomes were mortality and select morbidities (bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC)). Outcomes were compared between the baseline (January 2010 to May 2011) and post-intervention period (June 2012 to May 2013) within each comparison group. Results: Ninety-five hospitals were included with 4222 infants in the baseline period and 4186 infants in the post-intervention period. The Collaborative QI group had significantly reduced odds of developing BPD post-intervention (odds ratio (OR) 0.8, 95% confidence interval (CI) 0.65 to 0.99) or composite BPD-death (OR 0.83, 95% CI 0.69 to 1.00). In both the Collaborative QI and non-participants there were also reductions in IVH, severe IVH, composite severe IVH-death, severe ROP and composite severe ROP-death. Conclusion: Hospitals dedicated to improving delivery room practices can impact neonatal outcomes.

Sibutramine has a dual mode of action. It reduces food intake and attenuates the fall in metabolic rate associated with weight loss. The drug's neurochemical actions can also be distinguished from those of previous centrally acting anti-obesity agents. Clinical trials show that two out of three patients taking sibutramine lose >=5% weight and that the drug can enhance the maintenance of weight loss. Early weight loss predicts long-term success and can be used to guide clinical practice. To maximize the benefits of sibutramine, it is important that patients receive adjunctive diet and lifestyle therapy.

In 2005, for the first time in European history, an extraordinary Expert panel named 'The BSCG' (Bariatric Scientific Collaborative Group), was appointed through joint effort of the major European Scientific Societies which are active in the field of obesity management. Societies that constituted this panel were: IFSO - International Federation for the Surgery of Obesity, IFSO-EC - International Federation for the Surgery of Obesity - European Chapter, EASO - European Association for Study of Obesity, ECOG - European Childhood Obesity Group, together with the IOTF (International Obesity Task Force) which was represented during the completion process by its representative. The BSCG was composed not only of the top officers representing the respective Scientific Societies (four acting presidents, two past presidents, one honorary president, two executive directors), but was balanced with the presence of many other key opinion leaders in the field of obesity. The BSCG composition allowed the coverage of key disciplines in comprehensive obesity management, as well as reflecting European geographical and ethnic diversity. This joint BSCG expert panel convened several meetings which were entirely focused on guidelines creation, during the past two years. There was a specific effort to develop clinical guidelines, which will reflect current knowledge, expertize and evidence based data on morbid obesity treatment.

[...]the results of the current trials are available, my own preference, in the absence of participation in a current randomised trial, is to intubate infants of [= or <, slanted]26 weeks gestational age and administer surfactant within the first 30 min of life, followed by aggressive attempts to extubate the infant to CPAP or, preferably, nasal synchronous intermittent ventilation within the next 24-48 h. Further studies that include longer-term neurodevelopmental follow-up are required to determine the safety and effectiveness of the earlier use of CPAP without surfactant, the acceptance of higher PaCO2 (partial pressure of alveolar carbon dioxide) values and the use of higher levels of CPAP in ELBW infants with respiratory distress.