Secular trends in fitness,moderate-to-vigorous physical activity,and TV-viewing among first grade school children of Crete,Greece between 1992/93 and 2006/07

ObjectivesTo assess secular changes in physical fitness (PF), moderate-to-vigorous-physical activity (MVPA) and TV-viewing in 1st-grade children from Crete, Greece.DesignCross-sectional cohorts examined in academic years 1992/93 and 2006/07.MethodsTwo representative samples of children, aged 5.9–7.8 years, were studied during 1992/93 (N = 606) and 2006/07 (N = 361). PF (sit-and-reach, standing-broad-jump, sit-ups and 20 m-shuttle-run-test) was assessed by the European-PF test battery and MVPA by a physical activity (PA) questionnaire. Data on the frequency of TV-viewing was also collected.ResultsBetween 1992/93 and 2006/07, there was a significant increase in all fitness tests in both genders (P < 0.001) and in MVPA in boys (76.5 min/week vs. 38.7 min/week, P < 0.001). Time spent watching TV on weekdays was significantly more in both genders in 2006/07, compared to 1992/93 (P < 0.001). In 2006/07, active boys and active girls spent more time in MVPA than active boys and girls in 1992/93 (P < 0.001). Significantly higher proportions of boys and girls engaged in vigorous activities in 2006/07, than 1992/93 (P < 0.001 and P = 0.027, respectively).ConclusionsA significant increase in physical and cardiorespiratory fitness in both genders and MVPA in boys was observed in children from Crete between 1992/93 and 2006/07. The increase in weekday TV-viewing, despite being parallel to an increase in leisure-time MVPA, could have an unfavorable effect on health and should be tackled in future interventions in this population. Dietary, anthropometric and biochemical indices should also be investigated to assess their impact on the secular changes in physical fitness and activity observed in this sample of children.     

EP2306 and EP2302, two novel squalene synthase inhibitors, stimulate endothelial nitric oxide synthase expression in cultured endothelial cells.

EP2306 and EP2302 are two novel squalene synthase inhibitors with hypolipidemic, antiatherosclerotic, and antioxidant properties. In the present study, the authors investigated their effect on the expression and activity of endothelial nitric oxide synthase (eNOS) in cultured bovine aortic endothelial (BAE) cells and calf pulmonary artery endothelial (CPAE) cells. eNOS concentration was determined by immunoassay and eNOS activity by measuring the conversion of [(3)H]arginine to [(3)H]citrulline. Basal levels of eNOS in untreated BAE cells were 13.3 +/-1.6 ng/mg protein. Stimulation for 4 h with 30 microM of EP2306 or EP2302 resulted in increased eNOS protein level to 40% +/- 10% (p<.05) or 165% +/- 15% (p < .05) of unstimulated levels, respectively. Basal levels of eNOS in untreated CPAE cells were 3.4 +/- 0.4 ng/mg protein. Stimulation of CPAE cells for 4 h with 30 microM of EP2306 or EP2302 resulted in increased eNOS protein level to 195% +/- 24% (p < .05) and 152% +/- 19% (p < .05) of unstimulated levels, respectively. Despite their stimulatory action on eNOS expression, EP2300 compounds failed to induce any significant changes on eNOS enzymatic activity in BAE and CPAE cells. The finding that EP2300 compounds significantly increase the accumulation of eNOS in cultured endothelial cells sheds some light into their mechanism of action and supports a possible protective role of these compounds in atherosclerosis-related diseases.     

Alkaline phosphatase and its isoenzyme activity for the evaluation of bone metabolism in children receiving anticonvulsant monotherapy.

This study aimed to investigate whether carbamazepine, sodium valproate or phenobarbital as monotherapy in ambulatory epileptic children with adequate sun exposure have some effect on their bone metabolism based on the determination of total serum alkaline phosphatase (AP) levels and its bone isoenzyme activity. Blood samples were obtained from 118 epileptic children (37 on carbamazepine, 47 on sodium valproate and 34 on phenobarbital) and from corresponding healthy controls matched for age, gender and anthropometric parameters. AP and its liver, bone and intestinal isoenzyme levels, other common biochemical markers of bone and liver metabolism and drug levels were measured in the study participants. Patients on carbamazepine or phenobarbital had significantly elevated AP levels accompanied by increased bone and liver isoenzyme activity compared to controls. An increase of bone AP isoenzyme values, correlated with the duration of treatment ( r= 0.49, P= 0.002), was found in children on sodium valproate without, however, a concomitant significant elevation of total AP values. We conclude that children who receive antiepileptic drugs as monotherapy, even when residing in a Mediterranean country with adequate sunlight, may have their bone metabolism affected as indicated by the elevated levels of bone AP isoenzyme. This isoenzyme, but not total AP values, could therefore be used as a marker for the selection of patients who would be benefited by a thorough evaluation of their bone metabolism profile.     

Misoprostol for second trimester pregnancy termination in women with prior caesarean section

OBJECTIVE: To examine whether a previous caesarean section increases the risk for complications in women undergoing a mid-trimester pregnancy termination by labour induction. DESIGN: Retrospective analysis of case records between 1997 and 2002. SETTING: Fetal Medicine Unit of a large teaching hospital. POPULATION: One hundred and eight women with a previous caesarean section (study group) and 216 women without such a history (controls), who underwent a second trimester termination of pregnancy. METHODS: All the terminations were performed between 17 and 24 weeks of gestation by using 400 mug of oral administration of misoprostol in combination with 400 mug of intravaginal misoprostol. The same dose of intravaginal misoprostol was repeated every 6 hours for a maximum of five doses. MAIN OUTCOME MEASURES: Severe haemorrhage requiring blood transfusion, post-abortal infection, retained placenta and uterine rupture. RESULT: Complications occurred in 16 out of 108 women of the study group (15%) and in 26 out of 216 of the controls (12%), with only one ruptured uterus in the control group. CONCLUSION: We found no evidence that a previous caesarean delivery affects the incidence of complications when women with such a history undergo a mid-trimester pregnancy termination with misoprostol.     

Comparative Efficacy and Safety of Ultra-Long-Acting,Long-Acting,Intermediate-Acting,and Biosimilar Insulins for Type 1 Diabetes Mellitus: a Systematic Review and Network Meta-Analysis

BackgroundIncreasing availability of competing biosimilar alternatives makes it challenging to make treatment decisions. The purpose of this review is to evaluate the comparative efficacy and safety of ultra-long-/long-/intermediate-acting insulin products and biosimilar insulin compared to human/animal insulin in adults with type 1 diabetes mellitus (T1DM).MethodsMEDLINE, EMBASE, CENTRAL, and grey literature were searched from inception to March 27, 2019. Randomized controlled trials (RCTs), quasi-experimental studies, and cohort studies of adults with T1DM receiving ultra-long-/long-/intermediate-acting insulin, compared to each other, as well as biosimilar insulin compared to human/animal insulin were eligible for inclusion. Two reviewers independently screened studies, abstracted data, and appraised risk-of-bias. Pairwise meta-analyses and network meta-analyses (NMA) were conducted. Summary effect measures were mean differences (MD) and odds ratios (OR).ResultsWe included 65 unique studies examining 14,200 patients with T1DM. Both ultra-long-acting and long-acting insulin were superior to intermediate-acting insulin in reducing A1c, FPG, weight gain, and the incidence of major, serious, or nocturnal hypoglycemia. For fasting blood glucose, long-acting once a day (od) was superior to long-acting twice a day (bid) (MD - 0.44, 95% CI: - 0.81 to - 0.06) and ultra-long-acting od was superior to long-acting bid (MD - 0.73, 95% CI - 1.36 to - 0.11). For weight change, long-acting od was inferior to long-acting bid (MD 0.58, 95% CI: 0.05 to 1.10) and long-acting bid was superior to long-action biosimilar od (MD - 0.90, 95% CI: - 1.67 to - 0.12).ConclusionsOur results can be used to tailor insulin treatment according to the desired results of patients and clinicians and inform strategies to establish a competitive clinical market, address systemic barriers, expand the pool of potential suppliers, and favor insulin price reduction.PROSPERO RegistrationCRD42017077051Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06642-7.KEY WORDS: network meta-analysis, systematic review, insulin, biosimilar insulin, basal-bolus, diabetes mellitus, type 1 diabetes, T1DM     

Prospective study evaluating the predictability of need for retreatment with intravitreal ranibizumab for age-related macular degeneration

Purpose

To investigate the rhythm and predictability of the need for retreatment with intravitreal injections of ranibizumab for neovascular age-related macular degeneration (nAMD).

Methods

This prospective study enrolled 39 patients with treatment-naïve nAMD. After three loading doses of intravitreal ranibizumab, patients underwent an intensified follow-up for 12 months (initially weekly, then with stepwise increases to every 2 weeks and to monthly after each injection). Patients were retreated on an as-needed basis if any fluid or increased central retinal thickness (CRT) (>50μm) was found on spectral domain optical coherence tomography (OCT). Statistical analysis included patients who received at least two retreatments (five injections).

Results

A mean of 7.5 injections (range 0–12) were given between months 3 and 15. The mean visual acuity increased by 13.1 and 12.6 ETDRS letters at months 12 and 15 respectively. Two or more injection–retreatment intervals were found in 31 patients. The variability of their intra-individual intervals up to 14 weeks was small (SD 0–2.13 weeks), revealing a high regularity of the retreatment rhythm. The SD was correlated with the mean interval duration (r?=?0.89, p?<?0.001). The first interval was a good predictor of the following intervals (regression coefficient =0.81). One retreatment criterion was stable in 97 % of patients (cysts or subretinal fluid).

Conclusion

The results of this study demonstrate a high intra-individual predictability of retreatment need with ranibizumab injections for nAMD. These findings may be helpful for developing individualized treatment plans for maintained suppression of disease activity with a minimum of injections and visits.     

Effect of antiobesity medications in patients with type 2 diabetes mellitus

Obesity is considered as a major health problem, as its prevalence continuously rises worldwide. One of the common health consequences of obesity is type 2 diabetes mellitus. Therefore, antiobesity management is a prerequisite in treating diabetic patients. Lifestyle modifications combined with pharmacological agents appear to be an effective approach. Sibutramine is a serotonin–noradrenaline reuptake inhibitor, which acts centrally by promoting the feeling of satiety and decreasing caloric intake, thus resulting in weight loss. A potential association with cardiovascular side effects has been noted. Orlistat, a gastric and pancreatic lipase inhibitor, also achieves significant weight loss and improves glycaemic status, but it has gastrointestinal side effects. Rimonabant, the first endocannabinoid CB1 antagonist, is associated with weight reduction and it improves diabetic parameters; nevertheless, it is associated with psychiatric disorders; indeed, a recently conducted safety review led to the temporal suspension of its commercialization. The above-mentioned medications seem to be currently useful agents for treating obesity in patients with type 2 diabetes mellitus. Other medications used for diabetes management, such as exenatide, liraglutide and pramlintide, have also shown body weight reduction. Ongoing research is needed to scrutinize the precise impact of these agents in the daily clinical practice of management of obesity in patients with type 2 diabetes mellitus.