COLOR III: a multicentre randomised clinical trial comparing transanal TME versus laparoscopic TME for mid and low rectal cancer

Total mesorectal excision (TME) is an essential component of surgical management of rectal cancer. Both open and laparoscopic TME have been proven to be oncologically safe. However, it remains a challenge to achieve complete TME with clear circumferential resections margin (CRM) with the conventional transabdominal approach, particularly in mid and low rectal tumours. Transanal TME (TaTME) was developed to improve oncological and functional outcomes of patients with mid and low rectal cancer.An international, multicentre, superiority, randomised trial was designed to compare TaTME and conventional laparoscopic TME as the surgical treatment of mid and low rectal carcinomas. The primary endpoint is involved CRM. Secondary endpoints include completeness of mesorectum, residual mesorectum, morbidity and mortality, local recurrence, disease-free and overall survival, percentage of sphincter-saving procedures, functional outcome and quality of life. A Quality Assurance Protocol including centralised MRI review, histopathology re-evaluation, standardisation of surgical techniques, and monitoring and assessment of surgical quality will be conducted.The difference in involvement of CRM between the two treatment strategies is thought to be in favour of the TaTME. TaTME is therefore expected to be superior to laparoscopic TME in terms of oncological outcomes in case of mid and low rectal carcinomas

Assessment of the multidisciplinary education for a major change in clinical practice; a prospective cohort study

Background: New approaches are often introduced to the neonatal intensive care unit (NICU) and other areas of the health service in either a haphazard or cataclysmic fashion. The needs of staff education are often addressed incompletely or too late. Rarely is education assessed after the introduction of a major change. We changed the basis of our NICU respiratory support. We conducted a major educational and support program before this intervention. This study documented and assessed the educational components of this change in our health service provision. Methods: Senior medical and nursing staff attended training abroad and an education program was applied for one year prior to the change. Multidisciplinary educational support for doctors, nurses and allied health was continued after the change. Assessment was by anonymous questionnaire, prior to change, at one and at nine months. Our hypothesis was that dissatisfaction with education would be greatest at one month. Results: Both theory education and practical education aspects of the new approach were rated as good to very good and this did not change with time. Difficulty of applying the technique was rated as ambivalent initially but decreased significantly over 9 months until it was rated easy to very easy (p < 0.001). Over all, the change was rated by staff as beneficial, both at the end of the education period and at nine months, with no decrease at one month. Conclusion: If education and training reaches all staff, with a system of mutual and continued support, even large changes in clinical practice can be achieved without the dissatisfaction with the educational process that is often otherwise seen

Re-HEDP : pharmacokinetic characterization, clinical and dosimetric evaluation in osseous metastatic patients with two levels of radiopharmaceutical dose

BACKGROUND: A study for pain relief therapy with (188)Re-HEDP was done in patients with bone metastases secondary to breast and prostate cancer. MATERIALS AND METHODS: Patients received 1.3 or 2.2 GBq, in single or multiple doses. Platelets, white and red cells were evaluated during 11 weeks. Pharmacokinetic characterization was done from blood and urine samples for 5 patients along 24 hours. Urinary excretion was evaluated in other 16 patients during 6 hours. Bone uptake was estimated as remaining activity in whole body. Scintigraphic images were acquired at 2 and 24 hs post-administration. Absorbed dose in bone marrow was estimated with Mirdose3. Analgesics intake and pain score were daily recorded. Tumour markers (PSA, and Tn-structure) were monitored in 9 patients during 4 to 6 months. Single doses of low activity (1.3 GBq) were given to twelve patients. Nine patients received multiple doses. RESULTS: All except one patient had normal levels of platelets, white and red cells. Remaining dose in blood at 2 hours was 9%. Urinary elimination was 58%. Bone uptake at 24 hours was 43% (mean value; n = 5). No changes of the haematological parameters were detected along follow-up period. Pain relief was evidenced by decrease or supression of opioid analgesic and by subjective index. PSA showed a decrease in prostate cancer patients (n = 4). Tn-structure showed a significant increase after 4 to 8 months. CONCLUSION: Single or multiple dose scheme could be safely used, with administered activity of (188)Re-HEDP up to 60 mCi, with low bone marrow absorbed doses

Early signaling, referral, and treatment of adolescent chronic pain: a study protocol

<p>Abstract</p> <p>Background</p> <p>Chronic pain is prevalent among young people and negatively influences their quality of life. Furthermore, chronic pain in adolescence may persist into adulthood. Therefore, it is important early on to promote the self-management skills of adolescents with chronic pain by improving signaling, referral, and treatment of these youngsters. In this study protocol we describe the designs of two complementary studies: a signaling study and an intervention study.</p> <p>Methods and design</p> <p>The signaling study evaluates the Pain Barometer, a self-assessed signaling instrument for chronic pain in adolescents. To evaluate the feasibility of the Pain Barometer, the experiences of youth-health care nurses will be evaluated in semi-structured interviews. Also, we will explore the frequencies of referral per health-care provider. The intervention study evaluates Move It Now, a guided self-help intervention via the Internet for teenagers with chronic pain. This intervention uses cognitive behavioural techniques, including relaxation exercises and positive thinking. The objective of the intervention is to improve the ability of adolescents to cope with pain. The efficacy of Move It Now will be examined in a randomized controlled trial, in which 60 adolescents will be randomly assigned to an experimental condition or a waiting list control condition.</p> <p>Discussion</p> <p>If the Pain Barometer is proven to be feasible and Move It Now appears to be efficacious, a health care pathway can be created to provide the best tailored treatment promptly to adolescents with chronic pain. Move It Now can be easily implemented throughout the Netherlands, as the intervention is Internet based.</p> <p>Trial registration</p> <p>Dutch Trial Register NTR1926</p

The homocysteine controversy

Mild to moderate hyperhomocysteinemia has been identified as a strong predictor of cardiovascular disease, independent from classical atherothrombotic risk factors. In the last decade, a number of large intervention trials using B vitamins have been performed and have shown no benefit of homocysteine-lowering therapy in high-risk patients. In addition, Mendelian randomization studies failed to convincingly demonstrate that a genetic polymorphism commonly associated with higher homocysteine levels (methylenetetrahydrofolate reductase 677 C>T) is a risk factor for cardiovascular disease. Together, these findings have cast doubt on the role of homocysteine in cardiovascular disease pathogenesis, and the homocysteine hypothesis has turned into a homocysteine controversy. In this review, we attempt to find solutions to this controversy. First, we explain that the Mendelian randomization analyses have limitations that preclude final conclusions. Second, several characteristics of intervention trials limit interpretation and generalizability of their results. Finally, the possibility that homocysteine lowering is in itself beneficial but is offset by adverse side effects of B vitamins on atherosclerosis deserves serious attention. As we explain, such side effects may relate to direct adverse effects of the B-vitamin regimen (in particular, the use of high-dose folic acid) or to proinflammatory and proproliferative effects of B vitamins on advanced atherosclerotic lesions

Associations between interpregnancy interval and preterm birth by previous preterm birth status in four high-income countries: a cohort study.

OBJECTIVE: To investigate the effect of interpregnancy interval (IPI) on preterm birth (PTB) according to whether the previous birth was preterm or term. DESIGN: Cohort study. SETTING: USA (California), Australia, Finland, Norway (1980-2017). POPULATION: Women who gave birth to first and second (n = 3 213 855) singleton livebirths. METHODS: Odds ratios (ORs) for PTB according to IPIs were modelled using logistic regression with prognostic score stratification for potential confounders. Within-site ORs were pooled by random effects meta-analysis. OUTCOME MEASURE: PTB (gestational age <37 weeks). RESULTS: Absolute risk of PTB for each IPI was 3-6% after a previous term birth and 17-22% after previous PTB. ORs for PTB differed between previous term and preterm births in all countries (P-for-interaction ≤ 0.001). For women with a previous term birth, pooled ORs were increased for IPI <6 months (OR 1.50, 95% CI 1.43-1.58); 6-11 months (OR 1.10, 95% CI 1.04-1.16); 24-59 months (OR 1.16, 95% CI 1.13-1.18); and ≥ 60 months (OR 1.72, 95%CI 1.60-1.86), compared with 18-23 months. For previous PTB, ORs were increased for <6 months (OR 1.30, 95% CI 1.18-1.42) and ≥60 months (OR 1.29, 95% CI 1.17-1.42), but were less than ORs among women with a previous term birth (P < 0.05). CONCLUSIONS: Associations between IPI and PTB are modified by whether or not the previous pregnancy was preterm. ORs for short and long IPIs were higher among women with a previous term birth than a previous PTB, which for short IPI is consistent with the maternal depletion hypothesis. Given the high risk of recurrence and assuming a causal association between IPI and PTB, IPI remains a potentially modifiable risk factor for women with previous PTB. TWEETABLE ABSTRACT: Short versus long interpregnancy intervals associated with higher ORs for preterm birth (PTB) after a previous PTB

Long-term outcome of preterm infants treated with nasal continuous positive airway pressure

This study's aim was to assess neurodevelopmental and growth outcome until the age of 4 years of premature infants placed on early nCPAP, in the setting of the neonatal intensive care unit (NICU) and follow-up program of the Division of Neonatology of the Department of Pediatrics of the University Hospital, Lausanne, Switzerland. All consecutive inborn infants weighing &lt;1500 g or &lt;32 weeks of gestational age admitted to the NICU during two periods of 12 months-7.1996-6.1997 and 7.1998-6.1999-were compared before and after the systematic application of early nCPAP. Of 172 infants admitted to the NICU, 150 (87%) survived. 126 (84%) were tested at 6 months' corrected age, 121 (81%) at 18 months' corrected age, and 117 (78%) at the age of 4 years. Detailed perinatal data were collected. Follow-up included neurological examination, developmental testing and measurement of growth parameters. Statistical analyses were performed. Early application of nCPAP and avoidance of mechanical ventilation showed no adverse effects on neurodevelopment and growth. A significantly higher developmental quotient was found in the nCPAP group at 18 months' corrected age. Several trends were also noted in the nCPAP group with a decrease of intraventricular hemorrhage and in "abnormal neurodevelopment" at 6 months corrected age, a bigger head circumference at all different tested ages and a greater height at 6 and 18 months corrected ages. In conclusion, our study of developmental outcome documents the absence of any harmful effect of early application of nCPAP to treat respiratory failure in very low birthweight infants

Field testing and exploitation of genetically modified cassava with low-amylose or amylose-free starch in Indonesia

The development and testing in the field of genetically modified -so called- orphan crops like cassava in tropical countries is still in its infancy, despite the fact that cassava is not only used for food and feed but is also an important industrial crop. As traditional breeding of cassava is difficult (allodiploid, vegetatively propagated, outbreeding species) it is an ideal crop for improvement through genetic modification. We here report on the results of production and field testing of genetically modified low-amylose transformants of commercial cassava variety Adira4 in Indonesia. Twenty four transformants were produced and selected in the Netherlands based on phenotypic and molecular analyses. Nodal cuttings of these plants were sent to Indonesia where they were grown under biosafety conditions. After two screenhouse tests 15 transformants remained for a field trial. The tuberous root yield of 10 transformants was not significantly different from the control. Starch from transformants in which amylose was very low or absent showed all physical and rheological properties as expected from amylose-free cassava starch. The improved functionality of the starch was shown for an adipate acetate starch which was made into a tomato sauce. This is the first account of a field trial with transgenic cassava which shows that by using genetic modification it is possible to obtain low-amylose cassava plants with commercial potential with good root yield and starch quality

The TT genotype of methylenetetrahydrofolate reductase 677C>T polymorphism increases the susceptibility to pediatric ischemic stroke: meta-analysis of the 822 cases and 1,552 controls

The 677C>T polymorphism within methylenetetrahydrofolate reductase (MTHFR) gene is related to an elevated level of homocysteine. Thus it may be considered as a genetic risk factor in ischemic stroke. Apparently studies of this type of polymorphism in childhood stroke have shown conflicting results. We performed meta-analysis of all the data that are available in relation with MTHFR polymorphism and the risk of ischemic stroke in children. We searched PubMed (last search dated December 2010) using “MTHFR polymorphism”, “ischemic stroke” “child”, “children”, “pediatric stroke” as keywords and reference lists of studies and reviews on the topic. Finally, 15 case–control studies corresponded to the inclusion criteria for meta-analysis. These studies involved the total number of 822 children and adolescents after ischemic stroke and 1,552 control subjects. Fixed or random effects models were used depending on the heterogeneity between the studies. The association between ischemic stroke and 677C>T polymorphism within MTHFR gene was observed in three of the studies. The pooled analysis showed that TT genotype of MTHFR gene is more common in stroke patients than in controls (p = 0.0402, odds ratio = 1.57, 95 % confidence interval 1.02–2.41). The Egger’s test did not reveal presence of a publication bias. The results based on a sizeable group of cases and controls have proved that the 677C>T polymorphism in MTHFR gene is associated with the development of ischemic stroke in children

Obesity, smoking, alcohol consumption and years lived with disability: A Sullivan life table approach

Background: To avoid strong declines in the quality of life due to population ageing, and to ensure sustainability of the health care system, reductions in the burden of disability among elderly populations are urgently needed. Life style interventions may help to reduce the years lived with one or more disabilities, but it is not fully understood which life style factor has the largest potential for such reductions. Therefore, the primary aim of this paper is to compare the effect of BMI, smoking and alcohol consumption on life expectancy with disability, using the Sullivan life table method. A secondary aim is to assess potential improvement of the Sullivan method by using information on the association of disability with time to death. Methods. Data from the Dutch Permanent Survey of the Living Situation (POLS) 1997-1999 with mortality follow-up until 2006 (n = 6,446) were used. Using estimated relative mortality risks by risk factor exposure, separate life tables were constructed for groups defined in terms of BMI, smoking status and alcohol consumption. Logistic regression models were fitted to predict the prevalence of ADL and mobility disabilities in relationship to age and risk factor exposure. Using the Sullivan method, predicted age-specific prevalence rates were included in the life table to calculate years lived with disability at age 55. In further analysis we assessed whether adding information on time to death in both the regression models and the life table estimates would lead to substantive changes in the results. Results: Life expectancy at age 55 differed by 1.4 years among groups defined in terms of BMI, 4.0 years by smoking status, and 3.0 years by alcohol consumption. Years lived with disability differed by 2.8 years according to BMI, 0.2 years by smoking and 1.6 by alcohol consumption. Obese persons could expect to live more years with disability (5.9 years) than smokers (3.8 years) and drinkers (3.1 years). Employing information on time to death led to lower estimates of years lived with disability, and to smaller differences in these years according to BMI (2.1 years), alcohol (1.2 years), and smoking (0.1 years). Conclusions: Compared with smoking and drinking alcohol, obesity is most strongly associated with an increased risk of spending many years of life with disability. Although employing information on the relation of disability with time to death improves the precision of Sullivan life table estimates, the relative importance of risk factors remained unchanged