The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

A study of cleft lip/palate in a community in the South East of Ghana

The previous study in Wudoaba villages suggested that cleft lip and cleft palate (CL/CP) may be endemic in the Wudoaba cluster of villages in the Ketu South District of the Volta Region in South East Ghana. The study was to detect the prevalence of CL/CP in the Wudoaba communities and to investigate the factors associated with the causes of this malformation in the area. Two different interview-based questionnaires were designed to collect data over a period of 3 days from March 27 to 29, 2006. A purposive and accidental random sampling technique was used in the administering of the various questionnaires to the respondents. Data collected were recorded and analyzed with SPSS version 17.0. A total 99 respondents, with a mean age of 55.0 years, were interviewed. Out of it, 57.6% (n = 57) were related to their spouses: 54 first cousins and three other family relations. The prevalence of CL/CP is at least 6.3 per 1,000 people (i.e., 25/4,000). Majority (56.0%, n = 14) of the cleft cases were unilateral. Interviews revealed that genetic homogeneity and vitamin deficiencies in this community may be a causal factor for the high prevalence of CL/CP. This community provides clues suggesting that the magnitude of CL/CP may be larger than other studies and identifies the Wudoaba population as one that could be further studied to explore the underlying factors causing this congenital malformation

Quarantine for pandemic influenza control at the borders of small island nations

Background: Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure. Methods: Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered. Results: We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals). Conclusion: Quarantine atthe borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available). © 2009 Nishiura et al; licensee BioMed Central Ltd.published_or_final_versio

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Parental Depressive Feelings, Parental Support, and the Serotonin Transporter Gene as Predictors of Adolescent Depressive Feelings: A Latent Growth Curve Analysis

Parental support and parental depressive feelings are found to be associated with depressive feelings in adolescent boys and girls, but results are inconsistent. In addition, the 5-HTTLPR genotype has been found to interact with environmental stressors in predicting adolescents’ depressive feelings, but this has not been examined longitudinally. Therefore, the present study examined the relationships between parental support, parental depressive feelings, and adolescent depressive feelings. In addition, the relationships between the 5-HTTLPR genotype and adolescent depressive feelings were explored, as well as gene-environment interactions. Adolescents (N = 306; Girls = 53.3%; Mage T1 = 13.4) filled out questionnaires at five annual waves and provided saliva samples for DNA. Latent growth curve modelling (LGCM) was used to examine the baseline level and the change in depressive feelings over time. Maternal support was related to baseline levels of depressive feelings in girls, whereas paternal support was related to baseline levels in boys. Paternal depressive feelings were only related to boys’ depressive feelings at baseline, and maternal depressive feelings were not related to any outcome measures. Furthermore, no associations were found between 5-HTTLPR genotype and adolescent depressive feelings, and no gene-environment interactions emerged. Limitations of the study and implications of the findings are discussed

Effects of butter from mountain-pasture grazing cows on risk markers of the metabolic syndrome compared with conventional Danish butter: a randomized controlled study.

BACKGROUND: There is considerable interest in dairy products from low-input systems, such as mountain-pasture grazing cows, because these products are believed to be healthier than products from high-input conventional systems. This may be due to a higher content of bioactive components, such as phytanic acid, a PPAR-agonist derived from chlorophyll. However, the effects of such products on human health have been poorly investigated. OBJECTIVE: To compare the effect of milk-fat from mountain-pasture grazing cows (G) and conventionally fed cows (C) on risk markers of the metabolic syndrome. DESIGN: In a double-blind, randomized, 12-week, parallel intervention study, 38 healthy subjects replaced part of their habitual dietary fat intake with 39 g fat from test butter made from milk from mountain-pasture grazing cows or from cows fed conventional winter fodder. Glucose-tolerance and circulating risk markers were analysed before and after the intervention. RESULTS: No differences in blood lipids, lipoproteins, hsCRP, insulin, glucose or glucose-tolerance were observed. Interestingly, strong correlations between phytanic acid at baseline and total (P<0.0001) and LDL cholesterol (P=0.0001) were observed. CONCLUSIONS: Lack of effects on blood lipids and inflammation indicates that dairy products from mountain-pasture grazing cows are not healthier than products from high-input conventional systems. Considering the strong correlation between LDL cholesterol and phytanic acid at baseline, it may be suggested that phytanic acid increases total and LDL cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0134358