Long‐term effects of rapid weight gain in children,adolescents and young adults with appropriate birth weight for gestational age: the kiel obesity prevention study

Aim: This study investigates the effect of rapid weight gain in term children, adolescents and young adults born appropriate for gestational age. Methods: In all, 173 girls and 178 boys aged 6.1–19.9 (12.5 ± 3.1)years participated. Rapid weight gain (group 1) was defined as a change in weight‐SDS (standard deviation score) from birth till two years >0.67, ‘no change’ as ≥?0.67 and ≤0.67 (group 2) vs ‘slow weight gain’ as 90th age‐/sex‐specific BMI‐percentile was defined as overweight. Parental BMI, socio‐economic status and lifestyle were assessed as confounders. Results: A total of 22.8% gained weight rapidly, and 15.7% was overweight. Group 1 compared with group 2 and 3 subjects was taller, heavier and had a higher prevalence of overweight (girls/boys: 26.2%/28.9% vs 11.6%/19.0% vs 2.8%/5.0%; p < 0.01/p < 0.05). Concomitantly, a higher WC, %FM and FFM were observed. Rapid weight gain was positively associated with REE (adjusted for FFM) in boys (r = 0.26; p < 0.01), but not with cardio‐metabolic risk factors. Conclusion: Rapid weight gain was related to increases in height, weight, a higher prevalence of overweight and central fat distribution. In addition, rapid weight gain was related to a higher REE in boys, but not to cardio‐metabolic risk factors.     

血清骨唾液酸蛋白的生物变异性研究

目的　骨唾液酸蛋白（Ｂｏｎｅ ｓｉａｌｏｐｒｏｔｅｉｎ,简称ＢＳＰ）是由成骨细胞分泌的一种非胶原蛋白质,反映骨转换和骨形成的指标。最近研究认为：血清ＢＳＰ浓度可反映破骨细胞活性和骨吸收过程,也可能是一个骨吸收指标。本实验测定了血清ＢＳＰ在人体内的生物变异性。方法　采用ＲＩＡ 法测定了２９０例不同性别和年龄的正常人血清ＢＳＰ的正常值,血清ＢＳＰ的天－天变异性及２４ ｈ 生物周期。　结果　在儿童组血清ＢＳＰ正常水平明显高于成人组,其最高值在新生儿期和青春期。绝经后妇女其血清浓度比绝经前妇女水平明显升高（Ｐ＜ ０．０５）。血清ＢＳＰ在每天同一时间的波动范围在 ７．３％ 至１７．７％ （平均１１．７％ ）。２４ ｈ 内有一个明显的生物周期性变化,表现为峰值在凌晨４～８ 时,然后逐渐下降直到午后１４时为最低。其生物周期的最大波幅为±２０％ ,（平均血浓度为１０．５ ｎｇ／ｍ ｌ）。结论　血清ＢＳＰ反映了骨转换的生理变化与年龄有明显相关性,其血清水平２４ ｈ 内有一个明显的生物周期,而天与天之间变异性较小。     

Recommendations on managing lenvatinib and everolimus in patients with advanced or metastatic renal cell carcinoma

Introduction: There are several second-line treatment options for patients with renal cell carcinoma after first-line failure of a tyrosine kinase inhibitor, especially with the recent approvals of cabozantinib, nivolumab, and the lenvatinib plus everolimus combination. A lack of reliable biomarkers and an overall lack of prospective head-to-head comparisons make it a challenge to choose a second-line treatment in the clinic.

Areas covered: In this review/meta-opinion, we describe the safety profile of the lenvatinib plus everolimus combination in renal cell carcinoma. The combination of lenvatinib plus everolimus has achieved the highest rates of objective responses and the longest progression free and overall survival in cross-comparison trials. At the same time, the safety profile of this combination, including the rate of total and severe adverse events, the percentage of dose reductions required, and the rate of treatment discontinuation, was less favorable compared with available monotherapy options, suggesting that better management could help to maximize the activity of this combination while protecting patients from undue harm.

Expert opinion: Herein, we aim to postulate multidisciplinary recommendations on the advice to offer to patients and caregivers before starting treatment and how to manage the combination from the perspective of daily clinical practice.     

The usefulness of a free self-test for screening albuminuria in the general population: a cross-sectional survey

Background  

In this study we evaluated the usefulness of a free self-test for screening albuminuria in the general population.     

Dutch healthcare reform: did it result in performance improvement of health plans? A comparison of consumer experiences over time

Background  

Many countries have introduced elements of managed competition in their healthcare system with the aim to accomplish more efficient and demand-driven health care. Simultaneously, generating and reporting of comparative healthcare information has become an important quality-improvement instrument. We examined whether the introduction of managed competition in the Dutch healthcare system along with public reporting of quality information was associated with performance improvement in health plans.     

The M-OVIN study: does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate – a randomised controlled trial

Background

Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI.

Methods/Design

We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI.Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included.Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total).An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm).

Discussion

The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women.

Trial registration number

Netherlands Trial register NTR1449