Psychosocial development of full term singletons, born after preimplantation genetic diagnosis (PGD) at preschool age and family functioning: a prospective case-controlled study and multi-informant approach.

STUDY QUESTION: Do full term singletons born after preimplantation genetic diagnosis (PGD) differ in their psychosocial functioning from children born after intracytoplasmic sperm injection (ICSI) and spontaneous conceived controls (SC)? SUMMARY ANSWER: The psychosocial maturation process of 5-6-year-old PGD children is comparable between the three conception groups (PGD, ICSI and SC). WHAT IS ALREADY KNOWN: In general, a lot of research has been published regarding follow-up of children born after artificial reproductive technologies (ART), which mainly is reassuring. But the ART population itself is marked by broad diversity [IVF, ICSI, gamete donation, preimplantation genetic screening (PGS) or PGD] which complicates comparisons. Some literature concerning the socio-emotional development of PGD/PGS children is available and it suggests a normal maturation process. However, the complex reality of PGD families (e.g. safety of the technique and psychological burden of genetic histories) asks for an exclusive PGD sample with matched control groups and a multi-informant approach. STUDY DESIGN, SIZE, DURATION: Between April 2011 and May 2013, the psychosocial wellbeing of preschoolers and their families born after PGD was assessed in a prospective case-controlled, matched follow-up study, with a multi-informant approach. PARTICIPANTS/MATERIALS, SETTING, METHODS: A group of 47 PGD, 50 ICSI and 55 SC 5-6-year-old children participated in a follow-up study performed at the Centre for Medical Genetics of the Universitair Ziekenhuis Brussel (UZ Brussel). Assessments took place in the hospital and in kindergartens. Children performed the Bene-Anthony family relations test (FRT), yielding their perceptions upon family relationships. Parents and teachers completed the child behaviour checklist (CBCL) and Caregiver Teacher Report Form (C-/TRF), respectively. Parental and family functioning were measured by the NEO-FFi, the parenting stress index (PSI), the Greenberger Work-Parenting Investment Questionnaire and the Marlowe-Crowne Social Desirability Scale (MCSDS). Statistical analysis was performed by using analysis of covariance (ANCOVA). MAIN RESULTS AND THE ROLE OF CHANCE: No differences were detected between the psychosocial development of PGD children and the control groups. Parents did not differ in reporting problem behaviour and they were stricter than teachers. Concerning family functioning the ART parents scored comparable with each other. PGD and ICSI mothers were emotionally more stable [NEO-FFi Neuroticism/emotionality: P = 0.013, η(2) = 0.066; 95% confidence interval (CI) 95% (0.003;0.148)]. They experienced less parental stress in general [PSI, Total stress: P = 0.001, η(2) = 0.102, 95% CI (0.02;0.192)] and on different sublevels opposed to their SC counterparts. Yet ART mothers presented higher ratings on the NEO-FFi Conscientiousness [P = 0.011, η(2) = 0.064; 95% CI (0.003;0.144)] indicating a higher feeling of competence and goal directedness. Mediation analysis confirmed: PGD and ICSI mothers who experienced less family stress were emotionally more stable. A power analysis indicated that a sample with 152 children is sufficient to detect a medium size effect with 80% power using ANCOVA. LIMITATIONS, REASONS FOR CAUTION: The current sample comprised only Dutch speaking Caucasians, hence conclusions should be drawn cautiously. Future research should include larger groups, prematures, multiples and children from different cultural backgrounds. WIDER IMPLICATIONS OF THE FINDINGS: This current research is the first to compare PGD preschoolers with matched controls. Concerns about the behavioural effects on the offspring should not inhibit the use of PGD. Furthermore, our findings suggest that on the long run ART procedures might enhance personal resources of women to cope with family stress. These findings are reassuring for women who might feel insecure and anxious during their ART trajectory. STUDY FUNDING/COMPETING INTERESTS: This research project gained funding from the OZR (a grant by the Research group of the Vrije Universiteit Brussel), the FWO (Fonds Wetenschappelijk Onderzoek) and the Wetenschappelijk Fonds Willy Gepts. The UZ Brussel and the Centre of Medical Genetics received funding from pharmaceutical firms for data collection. UZ Brussel and the Centre for Medical Genetics have received many educational grants for organizing the data collection, from IBSA, Ferring, Organon, Shering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speaker's fees from Organon, Serono Symposia and Merck. The other authors have no competing interests. TRIAL REGISTRATION NUMBER: not applicable.

The vital force "reincarnated": modeling entelechy as a quantized spinning gyroscopic metaphor for integrated medicine.

The ancient concept of the Vital Force receives a modern incarnation as a metaphorical multidimensional spinning gyroscope. The consequences for a different understanding of health and disease are examined in the context of integrated medicine.

A quantum-like model of homeopathy clinical trials: importance of in situ randomization and unblinding.

BACKGROUND: The randomized controlled trial (RCT) is the 'gold standard' of modern clinical pharmacology. However, for many practitioners of homeopathy, blind RCTs are an inadequate research tool for testing complex therapies such as homeopathy. METHODS: Classical probabilities used in biological sciences and in medicine are only a special case of the generalized theory of probability used in quantum physics. I describe homeopathy trials using a quantum-like statistical model, a model inspired by quantum physics and taking into consideration superposition of states, non-commuting observables, probability interferences, contextuality, etc. RESULTS: The negative effect of blinding on success of homeopathy trials and the 'smearing effect' ('specific' effects of homeopathy medicine occurring in the placebo group) are described by quantum-like probabilities without supplementary ad hoc hypotheses. The difference of positive outcome rates between placebo and homeopathy groups frequently vanish in centralized blind trials. The model proposed here suggests a way to circumvent such problems in masked homeopathy trials by incorporating in situ randomization/unblinding. CONCLUSION: In this quantum-like model of homeopathy clinical trials, success in open-label setting and failure with centralized blind RCTs emerge logically from the formalism. This model suggests that significant differences between placebo and homeopathy in blind RCTs would be found more frequently if in situ randomization/unblinding was used.

A Systematic Review of Controlled Trials of Homeopathy in Bronchial Asthma.

Homeopathy is a controversial form of complementary therapy, but is widely practised to treat asthma. The aim of this systematic review is to evaluate the controlled trials of homeopathy in bronchial asthma. Relevant trials published between Jan 1, 1981, and Dec 31, 2016, were considered. Substantive research articles, conference proceedings, and master and doctoral theses were eligible. Methodology was assessed by Jadad's scoring, internal validity by the Coch-rane tool, model validity by Mathie's criteria, and quality of individualization by Saha's criteria. Sixteen trials were eligible. The majority were positive, especially those testing complex formulations. Methodological quality was diverse; 8 trials had "high" risk of bias. Model validity and individualization quality were compromised. Due to both qualitative and quantitative inadequacies, proofs supporting individualized homeopathy remained inconclusive. The trials were positive (evidence level A), but inconsistent, and suffered from methodological heterogeneity, "high" to "uncertain" risk of bias, incomplete study reporting, inadequacy of independent replications, and small sample sizes.

Identifiability of Components of Complex Interventions Using Factorial Designs.

OBJECTIVE: The aim of this contribution is to demonstrate how the component structure of a complex intervention (CI) can be efficiently exploited for study design and statistical analysis by using concepts of factorial designs. Many studies on CIs in complementary and alternative medicine exhibit the structure of factorial designs, where all possible combinations of the levels of two or more treatments occur together. In this contribution, the treatment arms of CI studies are explicitly viewed as factorial combinations of their components. Experimental design offers the general concept of identifiability of effects, that is, unique estimability of the components' effects from the observed data. For factorial designs, a simple cross table representation of the treatment arms can show the components or sums or interactions of components that are identifiable within a given study design. The question of identifiability arises particularly if some combinations of components are not observed (e.g., individualized homeopathic prescription without consultation). Study designs from published homeopathy studies are used for demonstration. CONCLUSIONS: CI studies should explicitly use an intervention's factorial component structure if it is inherent in the treatment arms being compared. In this way, investigators can avoid study designs from which the effects of interest cannot be uniquely estimated and improve the interpretation of estimated effects.

Utilization of indigenous systems of medicine & homoeopathy in India.

BACKGROUND & OBJECTIVE: Very little information is available on the utilization of Indian systems of medicine and homoeopathy (ISM&H) in India. A study was undertaken on the usage and acceptability of indigenous systems of medicine to provide estimate of utilization of different indigenous systems of medicine in the country along with the reasons for preferences as well as the cost of treatment. METHODS: The study covered 35 districts spreading over 19 States of the country. From 16 major States, two districts each were selected randomly one from the list of districts with high utilization level and another with low level of utilization. From other 3 States, one district each was selected randomly. From each selected district, 1000 households with at least one sick person were covered. This was achieved by selecting 50 Urban Frame Surveys (UFS)/villages and 20 sick persons each per village/UFS. Allocation of 50 First Stage Units (FSUs) among rural and urban sectors was made in proportion to rural-urban population of the district. From selected FSUs, 20 households with at least one sick person was selected randomly. The data were collected on the health seeking behaviour of persons who were sick (with common or serious ailments) in the last three months before survey including at the time of survey. RESULTS: About 45,000 sick persons from 33,666 households from 35 districts of the country were covered. The preference of ISM&H for common ailment was about 33 per cent while only 18 per cent preferred to use these systems in case of serious ailments in the country. The sick persons actually availing ISM&H treatment were about 14 per cent. Of those who preferred ISM&H, the reasons were mainly "no side effect" and low cost of treatment. Slow progress was the main reason for not preferring the indigenous systems. INTERPRETATION & CONCLUSION: The findings of this study showed that about 14 per cent sick persons utilizing indigenous system of medicine. Slow progress and non availability of practitioners were the main reasons for not preferring the ISM & H treatment.

Consumer preferences in social health insurance.

Allowing consumers greater choice of health plans is believed to be the key to high quality and low costs in social health insurance. This study investigates consumer preferences (361 persons, response rate 43%) for hypothetical health plans which differed in 12 characteristics (premium, deductibles, no-claim discount, extension of insurance and financial services, red tape involved, medical help-desk, choice of family physicians and hospitals, dental benefits, physical therapy benefits, benefits for prescription drugs and homeopathy). In 90% the health plan with the most attractive characteristics was preferred, indicating a predominantly rational kind of choice. The most decisive characteristics for preference were: complete dental benefits, followed by zero deductibles, and free choice of hospitals.

Bioprospecting: evolutionary implications from a post-olmec pharmacopoeia and the relevance of widespread taxa.

ETHNOPHARMACOLOGICAL RELEVANCE: "Nothing in biology makes sense except in the light of evolution" The historical legacy and relevance of ethnopharmacology in drug discovery is undisputed. Here we connect the parameters influencing the selection of plant derived medicines by human culture with the concept of evolution. AIM OF THE STUDY: In the present contribution we compare global data with local data and try to answer the questions, to what extent are the taxonomic clades included in indigenous pharmacopoeias associated with certain ailment groups, and to what extent can ecology and phylogeny, which we consider a proxy for chemical relatedness and convergence, account for the observed bias? MATERIALS AND METHODS: We use an approximated chi-square test (χ(2)) to check for associations between 12 ethnomedical use-categories and 15 taxonomical clades. With cluster analyses we test for correlations between phylogeny and use-categories. We compare the 67 drug-productive families identified by Zhu et al. with the medicinal flora of the Popoluca and the APG database and compare our results with the phylogenetic target classes evidenced by Zhu et al. Furthermore, we compare the medicinal flora of the Popoluca with the world's weeds (cf. Holm et al.) and discuss our results in relation to anthropological rationales for plant selection. RESULTS: The null-hypothesis "species from the 15 taxonomic clades are selected proportionally to their share in the treatment of the twelve organ- and symptom-defined use-categories" is rejected. The cluster dendrogram for the clades shows that the use patterns are to a certain extent associated with Angiosperm phylogeny. With the occurrence of 53 families the 67 drug-productive families are overrepresented in the regional flora of the Popoluca. The importance of these families in terms of their share is even more pronounced with the medicinal flora holding around 70% of all individual Popoluca informant responses. CONCLUSIONS: The overall phylogenetic use pattern is influenced by both the inherent pharmacological properties, which depend on phylogeny, biogeography, ecology and ultimately allelopathy, and on culture-specific perception of organoleptic properties. The comparison of the 67 drug-productive Viridiplantae families with the ethnopharmacopoeia of the Popoluca and the APG database, shows that "traditional" pharmacopoeias and plant-derived drugs are obtained from widespread and species-rich taxa. This is not a function of family size alone. We put forward the theory that as a function of evolution, widespread taxa contain a broader range of accumulated ecological information and response encoded in their genes relative to locally occurring taxa. This information is expressed through the synthesis of allelochemicals with a wide ecological radius, showing broad-spectrum biota-specific interactions, including the targeting of proteins of mammals and primates.

Do constitutional types really exist? A further study using grade of membership analysis.

'Constitutional types' are a feature of homeopathy. Constitutions are constellations of mental, physical and general features. We present results of a 152-item 'Constitutional Type Questionnaire' (CTQ), relating to 19 major constitutional remedies. Patients referred to the Royal London Homoeopathic Hospital (RLHH) were recruited from outpatient clinics. Each remedy was assigned eight associated features. Each item is rated as it applies to the subject most of the time on a five-point scale. Grade of Membership analysis (GOM) was used for evaluation of remedy profiles. Four hundred and forty-seven individuals provided usable data. Demographic data were collected. A nine pure type solution provided the best fit to the data. Few subjects had exclusive 'membership' of one pure type. There are some difficulties in interpretation; for instance some groups were characterised by the absence of 'constitutional' features. Some pure types are coherent, recognisable types. The results give some support to the homeopathic concept of constitution. CTQ results correlate quite well with the actual prescribing of homeopaths. Further validation with other cohorts is required and with refinement it might become a useful screening method. It cannot simulate complex information processing performed by homeopathic practitioners.

Comment on the paper, "Growth of yeast cultures as in vitro model for investigationg homoeopathic remedies"

A recent paper by Steffen repeating earlier work by Jones et al. failed to confirm any effect of potencies of Pulsatilla on the growth rate of cultures of Saccharomyces cerevisiae which had previously been reported. We find that using a more specific statistical test on the results given by Steffen it can be shown that these results contain almost the same periodicity with potency that Jones et al. reported, although only corresponding to a variation of +or- l.5//about the mean value