Randomised controlled trial of the effects of kefir on behaviour, sleep and the microbiome in children with ADHD: a study protocol.

INTRODUCTION: Current interventions for children with attention-deficit/hyperactivity disorder (ADHD) are primarily medication, behavioural therapy and parent training. However, research suggests dietary manipulations may provide therapeutic benefit for some. There is accumulating evidence that the gut microbiome may be atypical in ADHD, and therefore, manipulating gut bacteria in such individuals may help alleviate some of the symptoms of this condition. The aim of this study is to explore the effects of supplementation with kefir (a fermented dairy drink) on ADHD symptomatology, sleep, attention and the gut microbiome in children diagnosed with ADHD. METHODS AND ANALYSIS: A 6-week randomised, double-blind, placebo-controlled trial in 70 children aged 8-13 years diagnosed with ADHD. Participants will be recruited throughout the UK, through support groups, community groups, schools, social media and word of mouth. Children will be randomised to consume daily either dairy kefir or a placebo dairy drink for 6 weeks. The primary outcome, ADHD symptomatology, will be measured by The Strengths and Weakness of ADHD-symptoms and Normal-behaviour scale. Secondary outcomes will include gut microbiota composition (using shotgun metagenomic microbiome sequencing), gut symptomatology (The Gastrointestinal Severity Index questionnaire), sleep (using 7-day actigraphy recordings, The Child's Sleep Habits Questionnaire and Sleep Self Report questionnaire), inattention and impulsivity (with a computerised Go/NoGo test). Assessments will be conducted prior to the intervention and at the end of the intervention. Interaction between time (preintervention/postintervention) and group (probiotic/placebo) is to be analysed using a Mixed Model Analysis of Variances. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by St Mary's University Ethics Committee. Results will be disseminated through peer-reviewed publications, presentations to the scientific community and support groups. TRIAL REGISTRATION NUMBER: NCT05155696.

Recommendations in the design and conduction of randomised controlled trials in human and veterinary homeopathic medicine.

BACKGROUND: Randomised controlled trials (RCTs) are an established research method to investigate the effects of an intervention. Several recent systematic reviews and meta-analyses of RCTs with homeopathic interventions have identified shortcomings in design, conduct, analysis, and reporting of trials. Guidelines for RCTs in homeopathic medicine are lacking. OBJECTIVES: This paper aims to fill this gap in order to enhance the quality of RCTs in the field of homeopathy. METHODS: Identification of the homeopathy-specific requirements for RCTs by reviewing literature and experts' communications. Systematization of the findings using a suitable checklist for planning, conducting, and reporting RCTs, namely the SPIRIT statement, and high-quality homeopathy RCTs as examples. Cross-checking of the created checklist with the RedHot-criteria, the PRECIS criteria, and a qualitative evaluation checklist. Consideration of the REFLECT statement and the ARRIVE Guidelines 2.0 for veterinary homeopathy. RESULTS: Recommendations for future implementation of RCTs in homeopathy are summarized in a checklist. Alongside, identified useful solutions to the issues encountered when designing and conducting homeopathy RCTs are presented. CONCLUSIONS: The formulated recommendations present guidelines additional to those in the SPIRIT checklist, on how to better plan, design, conduct, and report RCTs in homeopathy.

Recommendations for Designing, Conducting and Reporting Clinical Observational Studies in Homeopathic Veterinary Medicine.

BACKGROUND: Clinical observational studies are an important methodological approach in human and veterinary research, examining and describing treatment experience with good external validity. There are currently few observational studies in the field of homeopathic veterinary medicine. AIM: The aim of the study was to develop recommendations for designing, conducting and reporting observational studies in homeopathic veterinary medicine. MATERIALS AND METHODS: A literature review was performed using various search strategies for identifying guidelines and checklist tools relevant for observational studies, veterinary research and homeopathy. Useful guidelines were selected. Prior recommendations for designing and conducting observational studies in human homeopathic medicine were supplemented with recommendations for homeopathic veterinary medicine that were evaluated by an expert panel. RESULTS: The veterinary extension of the Strengthening the Reporting of Observational Studies in Epidemiology - Veterinary (STROBE-Vet) statement was identified as a useful tool to improve the reporting quality of observational studies, and it has been supplemented here with additional recommendations that are applicable to homeopathy. STROBE-Vet is complemented in the literature by several reports, checklists and guidelines on veterinary medicine in general, such as the Checklist for One Health Epidemiological Reporting of Evidence (COHERE) and the Animal Health Surveillance Reporting Guidelines (AHSURED). Identified items that related to laboratory animal research were excluded as non-relevant to our study. CONCLUSION: Clinical observational studies are an important methodological approach, having currently unrealized potential in the field of homeopathic veterinary medicine. With relatively minor adjustments, the practical guidelines and checklists available to researchers in designing, conducting and reporting observational studies in human homeopathic medicine have been adapted for homeopathic veterinary medicine, for which high quality can be assured by implementing recommendations such as those in STROBE-Vet. With the emergence of the One Health concept, the COHERE checklist can be viewed with growing significance.

Test of a Homeopathic Algorithm for COVID-19: the Importance of a Broad Perspective.

BACKGROUND: Most of the symptoms of coronavirus disease 2019 (COVID-19) are covered by large repertory rubrics and hence many remedies have been proposed as "genus epidemicus". The aim of this study was to combine the information from various data collections to prepare a COVID-19 Bayesian mini-repertory/an algorithm-based application (app) and test it. METHODS: In July 2021, 1,161 COVID-19 cases from 100 practitioners globally were combined. These data were used to calculate "condition-confined" likelihood ratios (LRs) for 59 symptoms of COVID-19. Out of these, 35 symptoms of the 11 medicines that had at least 20 cases each were considered. The information was entered in a spreadsheet (algorithm) to calculate combined LRs of specific combinations of symptoms. The algorithm contained the medicines Arsenicum album, Belladonna, Bryonia alba, Camphora, Gelsemium sempervirens, Hepar sulphuris, Mercurius solubilis, Nux vomica, Phosphorus, Pulsatilla and Rhus toxicodendron. To test concordance, the doctors were then invited to re-enter the symptoms of their cases into this algorithm. RESULTS: The algorithm was re-tested on 358 cases, and concordance was seen in 288 cases. On analysis of the data, bias was noticed in the Merc group, which was therefore excluded from the algorithm. The remaining 10 medicines, representing 81.8% of all cases, were included in the preparation of the next version of the homeopathic mini-repertory and app. CONCLUSION: The Bayesian mini-repertory and app is based on qualitative clinical experiences of various doctors in COVID-19 and gives indications for specific medicines for common COVID-19 symptoms. It is freely available [English: https://hpra.co.uk/; Spanish: https://hpra.co.uk/es ] for further testing and utilization by the profession.

Adjunctive homeopathic treatment of hospitalized COVID-19 patients (COVIHOM): A retrospective case series.

BACKGROUND: and purpose. COVID-19 is a novel viral disease causing worldwide pandemia. The aim of this study was to describe the effect of adjunctive individualized homeopathic treatment delivered to hospitalized patients with confirmed symptomatic SARS-CoV-2 infection. PATIENT PRESENTATION: Thirteen patients with COVID-19 were admitted. Mean age was 73.4 ± 15.0 (SD) years. Twelve (92.3%) were speedily discharged without relevant sequelae after 14.4 ± 8.9 days. A single patient admitted in an advanced stage of septic disease died in hospital. A time-dependent improvement of relevant clinical symptoms was observed in the 12 surviving patients. Six (46.2%) were critically ill and treated in the intensive care unit (ICU). Mean stay at the ICU of the 5 surviving patients was 18.8 ± 6.8 days. In six patients (46.2%) gastrointestinal disorders accompanied COVID-19. CONCLUSION: The observations suggest that adjunctive homeopathic treatment may be helpful to treat patients with confirmed COVID-19 even in high - risk patients especially since there is no conventional treatment of COVID-19 available at present.

What families in the UK use to manage attention-deficit/hyperactivity disorder (ADHD): a survey of resource use.

OBJECTIVE: To identify interventions being used to manage attention-deficit/hyperactivity disorder (ADHD) in the UK. DESIGN: A survey within the Sheffield Treatments for ADHD Research project. A convenience sample of participants in the UK who consented to join an observational cohort were asked closed questions about medication, behavioural change programmes and service use, and an open-ended question about what else they used. SETTING: A broad variety of non-National Health Service, non-treatment seeking settings throughout the UK, including local authority organisations, schools, ADHD and autism spectrum condition support groups and social media. PARTICIPANTS: Families of children aged 5-18 with carer reported ADHD and Conners Global Index (CGI) T scores of 55+. RESULTS: Responses from 175 families were analysed. The mean age of the children was 10.21 (2.44), and two-thirds (n=114) had additional diagnoses. The majority used medications to manage ADHD (n=120) and had participated in a parenting class (n=130). Just over a quarter (28%, n=49) did not use ADHD medications, and used sleep medications. Just under half had consulted psychologists (n=83), and 32 had participated in other talking therapies such as psychotherapy, counselling and cognitive-behavioural therapy. A few used aids such as reward charts or fiddle toys (n=17) and participated in activities (mostly physical) (n=14). A substantial minority (78/175) had used non-mainstream treatments, the most popular being homoeopathy (n=32), nutritional interventions (n=21) and bodywork such as massage or cranial osteopathy (n=9). CONCLUSIONS: Families reported use of a wide variety of treatments to help with management of their children with ADHD in addition to their use of mainstream treatments.

Rethinking ADHD intervention trials: feasibility testing of two treatments and a methodology.

Attention deficit hyperactivity disorder (ADHD) is a lifelong condition associated with considerable costs. The long-term effectiveness and acceptability of treatments to improve outcomes remains in doubt. Long-term trials are needed comparing interventions with standard care and each other. The Sheffield Treatments for ADHD Research (STAR) project used the Trials within Cohorts (TwiCs) approach. A cohort of children with ADHD was recruited and outcomes collected from carers and teachers. A random selection was offered treatment by homoeopaths (hom) or nutritional therapists (NT). Their outcomes (Conners Global ADHD Index) were compared with those not offered interventions. The feasibility of the methods and interventions was assessed. The TwiCs approach was feasible with modifications. 144 participants were recruited to the cohort, 83 offered treatment, 72 accepted, and 50 attended 1+ appointments. Results according to carers assessments at 6 months were as follows: t = 1.08, p = .28 (- 1.48, 4.81) SMD .425 (hom); t = 1.71, p = .09 (- .347, 5.89), SMD = .388 (NT). Teachers' responses were too few and unstable. No serious treatment adverse events occurred.Conclusion: the STAR project demonstrated the feasibility of the TwiCs approach for testing interventions for children with ADHD. What is Known: • Attention deficit hyperactivity disorder (ADHD) is a lifelong condition associated with considerable costs to ADHD stakeholders. Children are at risk of negative outcomes and in need of pre-emptive strategies • The long-term effectiveness and acceptability of recommended treatments to improve outcomes remains in doubt What is New: • A small-scale test of the design demonstrated that the Trials within Cohorts (TwiCs) approach is feasible and can make a useful contribution regarding testing the effectiveness of interventions for children with ADHD to improve long-term negative outcomes • Treatment by homoeopaths and nutritional therapists may offer novel opportunities to improve outcomes.

Protocol for the STAR (Sheffield Treatments for ADHD) project: an internal pilot study assessing the feasibility of the Trials within Cohorts (TwiCs) design to test the effectiveness of interventions for children with ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common and growing problem and a leading cause of child referrals to Child and Adult Mental Health Services (CAMHS). It is a drain on resources across nationally funded support agencies and associated with negative outcomes such as early criminality, school disruption and antisocial behaviour. Mainstream interventions (pharmacological and behavioural) demonstrate effectiveness whilst implemented, but are costly, often have unwanted side effects and do not appear to be affecting long-term outcomes.Development of a robust evidence base for the effectiveness of current and novel interventions and their impact over the long term is required. The aim of the Sheffield Treatments for ADHD Research (STAR) project is to facilitate a rigorous evidence base in order to provide information about the comparative (cost) effectiveness and acceptability of multiple interventions to key stakeholders. METHODS: The Trials within Cohorts (TwiCs) design was used to build a cohort of children with a diagnosis of ADHD and conduct a three-armed pilot trial of the clinical and cost effectiveness of two novel interventions: (a) treatment by nutritional therapists and (b) treatment by homoeopaths, compared to (c) treatment as usual.Participants are recruited to the STAR long-term observational cohort, and their outcomes of interest (ADHD symptoms, health-related quality of life, school disruption, resource use and criminality) are measured every 6 months by carers and (blinded) teachers. Two promising interventions were identified for the first randomised controlled trial embedded in the cohort. A random selection of eligible participants is offered treatments (a) and (b). The outcomes of those offered treatment are compared to those not offered treatment using intention to treat (ITT) analysis.The feasibility of recruiting to the cohort and the trial, delivering the interventions, the effectiveness of the interventions and the appropriateness, sensitivity and collectability of outcomes is trialled. DISCUSSION: The results of this trial will provide information on the feasibility of the TwiCs design to facilitate multiple trials of potential interventions for children with ADHD, and the acceptability, clinical and cost effectiveness of two potential interventions for ADHD to ADHD stakeholders including service providers. Future stages of the STAR project will test other treatments informed by the results in stage 1. TRIAL REGISTRATION: ISRCTN number 17723526. 10.1186/ISRCTN17723526. Date assigned 27/4/15.

Prevalence of homeopathy use by the general population worldwide: a systematic review.

AIM: To systematically review surveys of 12-month prevalence of homeopathy use by the general population worldwide. METHODS: Studies were identified via database searches to October 2015. Study quality was assessed using a six-item tool. All estimates were in the context of a survey which also reported prevalence of any complementary and alternative medicine use. RESULTS: A total of 36 surveys were included. Of these, 67% met four of six quality criteria. Twelve-month prevalence of treatment by a homeopath was reported in 24 surveys of adults (median 1.5%, range 0.2-8.2%). Estimates for children were similar to those for adults. Rates in the USA, UK, Australia and Canada all ranged from 0.2% to 2.9% and remained stable over the years surveyed (1986-2012). Twelve-month prevalence of all use of homeopathy (purchase of over-the-counter homeopathic medicines and treatment by a homeopath) was reported in 10 surveys of adults (median 3.9%, range 0.7-9.8%) while a further 11 surveys which did not define the type of homeopathy use reported similar data. Rates in the USA and Australia ranged from 1.7% to 4.4% and remained stable over the years surveyed. The highest use was reported by a survey in Switzerland where homeopathy is covered by mandatory health insurance. CONCLUSIONS: This review summarises 12-month prevalence of homeopathy use from surveys conducted in eleven countries (USA, UK, Australia, Israel, Canada, Switzerland, Norway, Germany, South Korea, Japan and Singapore). Each year a small but significant percentage of these general populations use homeopathy. This includes visits to homeopaths as well as purchase of over-the-counter homeopathic medicines.

A comparative consecutive case series of 20 children with a diagnosis of ADHD receiving homeopathic treatment, compared with 10 children receiving usual care.

20 consecutively enrolled children age 5-16 with Attention Deficit Hyperactivity Disorder (ADHD) received treatment by a homeopath (8 consultations and individualized remedies) for one year. Ten subsequently enrolled children received similar time and attention for 4 months. The study explored optimum treatment protocols; the effectiveness, deliverability and acceptability of treatment; and the feasibility of outcome measurement and recruitment. Parents completed Conners' Parent Rating Scale, Revised Long Version ( CPRS-R: L) every 4 months, from which DSMIV total scores were extracted; and Measure Your Own Medical Outcome Profile (MYMOP) every consultation. An interaction between time (baseline/4 months) and group (treatment/non-treatment) was found .756 F (1,28)=9.06, p=0.005. The intervention was associated with statistically significant improvements in treated children over the year: CPRS-R: L (t (18)=4.529, p≤0.000); MYMOP (t (18)=6.938, p≤0.000). Mean DSMIV total t scores decreased at each time point: baseline: 85 (SD 5.1); 4 months 76.2 (SD 10.9); and 12 months 71.5 (SD 12.77). Recruitment of control participants was problematic. Recruitment to treatment was feasible via ADHD support groups, charities, police support agencies and social services, not schools or NHS services. Attending appointments was problematic for some participants, but home visits did not improve uptake. The best venue was a familiar clinic. Some participants took medicines inappropriately, but generally taking homeopathic remedies was acceptable and well implemented. CPRS-R: L (80 items) was problematic for some parents. MYMOP was preferred by parents but not acceptable to stakeholders. In this small consecutive sample the intervention was associated with improvements in criminality, anger and children with a concomitant diagnosis of Autism Spectrum Disorder ASD. Treatment by a homeopath was associated with sustained, increasing improvements and the intervention was acceptable to participants. More methodically rigorous research is warranted. "We recommend that future research in this area uses comparative effectiveness randomised controlled trial designs. We also recommend that these trials measure outcomes of relevance to stakeholder needs - the people and services who care for those with ADHD - parents, teachers and social workers and the criminal justice system".