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P Fisher

Publications and source records attributed to P Fisher.

At least 19 recordsLinked to original sources

A systematic review of the quality of homeopathic pathogenetic trials published from 1945 to 1995.

BACKGROUND: The quality of information gathered from homeopathic pathogenetic trials (HPTs), also known as 'provings', is fundamental to homeopathy. We systematically reviewed HPTs published in six languages (English, German, Spanish, French, Portuguese and Dutch) from 1945 to 1995, to assess their quality in terms of the validity of the information they provide. METHODS: The literature was comprehensively searched, only published reports of HPTs were included. Information was extracted by two reviewers per trial using a form with 87 items. Information on: medicines, volunteers, ethical aspects, blinding, randomization, use of placebo, adverse effects, assessments, presentation of data and number of claimed findings were recorded. Methodological quality was assessed by an index including indicators of internal and external validity, personal judgement and comments of reviewers for each study. RESULTS: 156 HPTs on 143 medicines, involving 2815 volunteers, produced 20,538 pathogenetic effects (median 6.5 per volunteer). There was wide variation in methods and results. Sample size (median 15, range 1-103) and trial duration (mean 34 days) were very variable. Most studies had design flaws, particularly absence of proper randomization, blinding, placebo control and criteria for analysis of outcomes. Mean methodological score was 5.6 (range 4-16). More symptoms were reported from HPTs of poor quality than from better ones. In 56% of trials volunteers took placebo. Pathogenetic effects were claimed in 98% of publications. On average about 84% of volunteers receiving active treatment developed symptoms. The quality of reports was in general poor, and much important information was not available. CONCLUSIONS: The HPTs were generally of low methodological quality. There is a high incidence of pathogenetic effects in publications and volunteers but this could be attributable to design flaws. Homeopathic medicines, tested in HPTs, appear safe. The central question of whether homeopathic medicines in high dilutions can provoke effects in healthy volunteers has not yet been definitively answered, because of methodological weaknesses of the reports. Improvement of the method and reporting of results of HPTs are required. REFERENCES: References to all included RCTs are available on-line at.

Homeopathy↗

Reporting data on homeopathic treatments (RedHot): a supplement to CONSORT.

When homeopathy is tested in clinical trials, understanding and appraisal is likely to be improved if published reports contain details of prescribing strategies and treatments. An international Delphi panel was convened to develop consensus guidelines for reporting homeopathic methods and treatments. The panel agreed 28 treatment- and provider-specific items that supplement the Consolidated Standards of Reporting Trials (CONSORT) Statement items 2, 3, 4 and 19. The authors recommend these for adoption by authors and journals when reporting trials of homeopathy.

Consensus↗

Homeopathy for anxiety and anxiety disorders: a systematic review of the research.

OBJECTIVE: To conduct a systematic review of the clinical research evidence on homeopathy in the treatment of anxiety and anxiety disorders. METHODS: A comprehensive search of major biomedical databases: MEDLINE, EMBASE, ClNAHL, PsycINFO, Cochrane Library; and of specialist complementary and alternative medicine (CAM) databases: AMED, CISCOM and Hom-Inform was conducted. Efforts were made to identify unpublished and ongoing research using relevant sources and experts in the field. Relevant research was categorised by study type and appraised according to study design. Clinical commentaries were obtained for studies reporting clinical outcomes. RESULTS: Eight randomised controlled studies were identified. The types of anxiety and anxiety disorders studied were test anxiety, generalised anxiety disorder and anxiety related to medical or physical conditions such as cancer or surgical procedures. Single case reports/studies were the most frequently encountered study type but other study types including uncontrolled trials/case series and surveys were also found. No relevant qualitative research was identified. CONCLUSIONS: A comprehensive search demonstrates that the evidence on the benefit of homeopathy in anxiety and anxiety disorders is limited. A number of studies of homeopathy in such conditions were located but the randomised controlled trials report contradictory results, are underpowered or provide insufficient details of methodology. Several uncontrolled and observational studies reported positive results including high levels of patient satisfaction but because of the lack of a control group, it is difficult to assess the extent to which any response is due to homeopathy. Adverse effects reported appear limited to 'remedy reactions' and included temporary worsening of symptoms and reappearance of old symptoms. On the basis of this review it is not possible to draw firm conclusions on the efficacy or effectiveness of homeopathy for anxiety. However, surveys suggest that homeopathy is quite frequently used by people suffering from anxiety. If shown to be effective, it is possible that homeopathy may have benefits in terms of adverse effects and acceptability to patients. Consequently, further investigation is indicated. Future research should be of pragmatic design and include qualitative studies.

Antidepressive Agents↗

The feasibility of a randomised, placebo-controlled clinical trial of homeopathic treatment of depression in general practice.

UNLABELLED: Depression is common in general practice and lack of concordance is an important problem in its treatment. Homeopathy has few side effects and is generally associated with good compliance. We report a study investigating the feasibility of a trial to compare the effectiveness of homeopathy with a conventional antidepressant and placebo. OBJECTIVES: To assess the feasibility of a general practice-based clinical trial comparing the effectiveness of individualised homeopathic treatment vs Fluoxetine (Prozac) vs placebo in the treatment of major depressive episodes of moderate severity. DESIGN: Randomised, double-dummy, double-blind parallel group clinical trial. SETTING: Lower Clapton Group Practice, East London. METHOD: Patients were recruited through their general practitioners as they presented during a 9 month period. Recruitment target was 30 patients. Eligibility was confirmed by a consultant psychiatrist using standard criteria (DSM-IV) and instruments Hamilton Depression Scale (HAMD). Suicidal and psychotic patients were excluded, additional precautions against suicide were incorporated. There was a 1 week run-in period and patients showing spontaneous improvement were excluded. Homeopathic treatment was prescribed by a GP qualified in homeopathy, from a 'limited list' of 30 homeopathic medicines, with the help of decision support software. Patients were randomised to receive verum Fluoxetine and placebo homeopathy, or verum homeopathy and placebo Fluoxetine, or placebo homeopathy and placebo Fluoxetine. Treatment duration was 12 weeks. The outcomes were: adverse drug reactions, clinical global impression (CGI); HAMD; mini international psychiatric Interview; Pittsburgh sleep quality index; Side-effects checklist; Short Form 12; treatment credibility questionnaire; work and social disability scale. The primary outcome measures were HAMD and CGI. RESULTS: A recruitment calculation indicated that over 230 suitable patients would be expected to attend the practice during the recruitment phase. Thirty one patients were referred for possible inclusion in the trial by their GPs. Twenty three met the entry criteria, 11 were randomised and 6 completed the study. Of the completers, one received homeopathy, 2 placebo and 3 Fluoxetine. CONCLUSIONS: A trial of this design in general practice is not feasible, because of recruitment difficulties, many of them linked to patient preference. Different approaches are required to recruit adequate patient numbers to trials of this sort.

Adult↗

Homeopathy for depression: a systematic review of the research evidence.

OBJECTIVE: To systematically review the research evidence on the effectiveness of homeopathy for the treatment of depression and depressive disorders. METHODS: A comprehensive search of major biomedical databases including MEDLINE, EMBASE, CINAHL, PsycINFO and the Cochrane Library was conducted. Specialist complementary and alternative medicine (CAM) databases including AMED, CISCOM and Hom-Inform were also searched. Additionally, efforts were made to identify unpublished and ongoing research using relevant sources and experts in the field. Relevant research was categorised by study type and appraised according to study design. Clinical commentaries were obtained for studies reporting clinical outcomes. RESULTS: Only two randomised controlled trials (RCTs) were identified. One of these, a feasibility study, demonstrated problems with recruitment of patients in primary care. Several uncontrolled and observational studies have reported positive results including high levels of patient satisfaction but because of the lack of a control group, it is difficult to assess the extent to which any response is due to specific effects of homeopathy. Single-case reports/studies were the most frequently encountered clinical study type. We also found surveys, but no relevant qualitative research studies were located.: Adverse effects reported appear limited to 'remedy reactions' ('aggravations') including temporary worsening of symptoms, symptom shifts and reappearance of old symptoms. These remedy reactions were generally transient but in one study, aggravation of symptoms caused withdrawal of the treatment in one patient. CONCLUSIONS: A comprehensive search for published and unpublished studies has demonstrated that the evidence for the effectiveness of homeopathy in depression is limited due to lack of clinical trials of high quality. Further research is required, and should include well-designed controlled studies with sufficient numbers of participants. Qualitative studies aimed at overcoming recruitment and other problems should precede further RCTs. Methodological options include the incorporation of preference arms or uncontrolled observational studies. The highly individualised nature of much homeopathic treatment and the specificity of response may require innovative methods of analysis of individual treatment response.

Control Groups↗

Cloning: eight years after Dolly.

It is now 8 years since the birth of Dolly, the first animal produced by nuclear transfer using a donor cell population established from an adult animal. During this time, the technique of nuclear transfer has been successfully applied to a range of mammalian species for the production of offspring using a plethora of donor cell types derived from both foetal and adult tissues. In addition, when coupled with genetic manipulation of the donor cells, transgenic offspring have been produced with a range of genetic modifications including gene knockouts and gene knockings. Despite the apparent successes of the technology, the efficiency of development to live offspring has remained low and developmental abnormalities still occur. The objectives of this paper are to review some of the successes and failures of the nuclear transfer procedure since the production of Dolly. In particular, we will review the major steps in the procedure and discuss studies from our laboratory and others which have modified the procedure in ways which may impact on development.

Animals↗

Acupuncture of chronic headache disorders in primary care: randomised controlled trial and economic analysis.

OBJECTIVES: To determine the effects of a policy of using acupuncture, compared with a policy of avoiding acupuncture, on headache in primary care patients with chronic headache disorders. The effects of acupuncture on medication use, quality of life, resource use and days off sick in this population and the cost-effectiveness of acupuncture were also examined. DESIGN: Randomised, controlled trial. SETTING: General practices in England and Wales. PARTICIPANTS: The study included 401 patients with chronic headache disorder, predominantly migraine. INTERVENTIONS: Patients were randomly allocated to receive up to 12 acupuncture treatments over 3 months or to a control intervention offering usual care. MAIN OUTCOME MEASURES: Outcome measures included headache score; assessment of Short Form 36 (SF-36) health status and use of medication at baseline, 3 months and 12 months; assessment of use of resources every 3 months; and assessment of incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: Headache score at 12 months, the primary end-point, was lower in the acupuncture group than in controls. The adjusted difference between means was 4.6. This result was robust to sensitivity analysis incorporating imputation for missing data. Patients in the acupuncture group experienced the equivalent of 22 fewer days of headache per year. SF-36 data favoured acupuncture, although differences reached significance only for physical role functioning, energy and change in health. Compared with controls, patients randomised to acupuncture used 15% less medication, made 25% fewer visits to GPs and took 15% fewer days off sick. Total costs during the 1-year period of the study were on average higher for the acupuncture group than for controls because of the acupuncture practitioners' costs. The mean health gain from acupuncture during the year of the trial was 0.021 QALYs, leading to a base-case estimate of GBP9180 per QALY gained. This result was robust to sensitivity analysis. Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial. CONCLUSIONS: The study suggests that acupuncture leads to persisting, clinically relevant benefits for primary care patients with chronic headache, particularly migraine. It is relatively cost-effective compared with a number of other interventions provided by the NHS. Further studies could examine the duration of acupuncture effects beyond 1 year and the relative benefit to patients with migraine with compared to tension-type headache. Trials are also warranted examining the effectiveness and cost-effectiveness of acupuncture in patients with headache receiving more aggressive pharmacological management.

Acupuncture↗

Homeopathy for dementia.

BACKGROUND: Dementia is a common illness in older people and has major implications for individuals with the disease, their carers and society. A meta-analysis of population based studies in Europe found the prevalence of dementia in individuals over 65 to be 6.4%. Homeopathy (also spelt "homoeopathy") is a popular form of "complementary" or "alternative" treatment. Some studies have found evidence for efficacy of homeopathic treatment for some conditions, but any mechanism of action of the ultra molecular dilutions used in homeopathy is not comprehensible in terms of current scientific concepts. OBJECTIVES: To evaluate the effectiveness and safety profile of homeopathically prepared medications used in treating dementia, as established by randomized controlled trials. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 May 2002 using the terms alum*, homeop*, "nat sulph" and "natrum sulphate". This Register contains records from all major medical databases. In addition the reviewers searched CISCOM, AMED and Hom-Inform. Leading homeopathic researchers, practitioners and manufacturers were also contacted. SELECTION CRITERIA: All types of randomized controlled trials with a sample size of more than 20 were considered. DATA COLLECTION AND ANALYSIS: The database searches resulted in one trial being identified. After examining the abstract, a paper copy was obtained and independently assessed for inclusion by RM and JW. MAIN RESULTS: There were no studies that fulfilled the criteria for inclusion and no data to present. REVIEWER'S CONCLUSIONS: In view of the absence of evidence it is not possible to comment on the use of homeopathy in treating dementia. The extent of homeopathic prescribing for people with dementia is not clear and so it is difficult to comment on the importance of conducting trials in this area.

Dementia↗

NHS patients' perspective on complementary medicine: a survey.

OBJECTIVES: To examine patients' reasons for seeking complementary and alternative medicine (CAM) in the National Health Service, including the nature and duration of the patient's main health problem, the impact of CAM on this, satisfaction with clinical care, and usage of conventional prescription medication. DESIGN: Survey (n=499). SETTING: Out-patient Department, The Royal London Homeopathic Hospital, a National Health Service facility dedicated to CAM. RESULTS: Five hundred and six questionnaires were returned, 499 were analysed. Patients' most frequent reasons for seeking CAM were that other treatment had not helped, and concerns about or experience of adverse treatment reactions. Two hundred and ninety-seven patients (63%) had had their main problem for more than 5 years. Musculoskeletal system problems were the most frequent diagnostic group (n=151, 32%). Satisfaction with clinical care was high (443/490: 90%). Three hundred and eighty patients (81%) indicated their main problem had improved very much, moderately or slightly. Of the 262 patients who had been taking prescription medicines when they first attended, 76 (29%) had stopped, and 84 (32%) had reduced their intake. CONCLUSIONS: The results suggest that orthodox medicine is not meeting the needs of some patients and that CAM may wholly or partly substitute for conventional medicines. Most patients indicated their problem had improved with CAM. Implications for future research are discussed.

Adolescent↗

Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB- Lepr (db)) and obese (DBA- Lep (ob)) mice.

AIMS: Our goal was to identify genetic variants that determine the response to insulin resistance and hyperglycaemia. This report documents the diabetes syndrome of two new congenic strains of mice generated by the transfer of the Lepr(db) mutation to the FVB/NJ strain and the Lep(ob) mutation to the DBA/2J strain. METHODS: Mice were characterised by measures of blood metabolites and hormones along with challenges with glucose and insulin injections. Histological examinations of the endocrine pancreas and the kidneys were also carried out. RESULTS: Obese mice of the FVB-db congenic strain show long-term hyperglycaemia that is primarily due to severe insulin resistance. The hyperglycaemia in the fed state persists despite escalating secretion of insulin and massive increase of pancreatic beta cells. Obese FVB-db mice show evidence of mesangial matrix expansion, a hallmark of diabetic nephropathy. Leptin-deficient mice of the DBA-ob strain have variable obesity-diabetes. In mice with high insulin (>10 ng/ml), DBA-ob/ob mice maintain their increased adiposity and have a large increase in beta-cell number. In mice with low insulin (<1 ng/ml) DBA-ob/ob mice have greatly diminished adiposity. These mice have atrophied islets with evidence of increased beta-cell neogenesis from the ductal epithelium. CONCLUSIONS: The strain-specific responses suggest the existence of genetic variants that control insulin sensitivity and beta-cell responses in the strains described in this report. These new models of obesity-diabetes should prove useful in dissecting the genetic control of beta-cell responses to hyperglycaemia and insulin resistance.

Animals↗

Accruing large numbers of patients in primary care trials by retrospective recruitment methods.

There is a need for large scale, pragmatic trials of complementary and alternative medicine in a primary care setting to answer questions about the 'real world' effectiveness of such methods. Randomisation and treatment in such trials should be prospective, but retrospective recruitment is possible, especially in chronic conditions. This involves contacting patients who have previously consulted their GP (identified through GP database searches) rather than encouraging GPs to refer patients as they present. We describe a prospective randomised trial of acupuncture for chronic headache, currently underway, as an example of retrospective recruitment. A pilot study of recruitment and recruitment modelling was undertaken. The target sample size was 300, 26% (n = 36) of general practices approached took part in the study, 32 completed the required database search. Practices used diagnostic term searches, prescription searches, or a combination of both. On average 1.7% of the total practice populations were identified as headache consulters, letters were sent to 4128 patients. 12% of identified patients were randomised (n = 401). Retrospective recruitment methods are feasible for CAM trials in chronic, stable conditions modelling can provide accurate data for planning such studies. Retrospective recruitment can be more efficient than prospective, further research is required on the generalisibility of results from populations recruited in this way.

Acupuncture Therapy↗

Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial.

Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load. A randomized double-blind trial was conducted to determine whether six dowsing homeopaths were able to distinguish between Bryonia in a 12c potency and placebo by use of dowsing alone. The homeopathic medicine Bryonia was correctly identified in 48.1% of bottle pairs (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689). These results, wholly negative, add to doubts whether dowsing in this context can yield objective information.

Confidence Intervals↗

An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice.

PTEN phosphatase acts as a tumor suppressor by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. It is unclear which downstream components of this pathway are necessary for oncogenic transformation. In this report we show that transformed cells of PTEN(+/-) mice have elevated levels of phosphorylated Akt and activated p70/S6 kinase associated with an increase in proliferation. Pharmacological inactivation of mTOR/RAFT/FRAP reduced neoplastic proliferation, tumor size, and p70/S6 kinase activity, but did not affect the status of Akt. These data suggest that p70/S6K and possibly other targets of mTOR contribute significantly to tumor development and that inhibition of these proteins may be therapeutic for cancer patients with deranged PI3K signaling.

Alleles↗

Development of mammary adenocarcinomas by tissue-specific knockout of Brca2 in mice.

Cre-mediated deletion of exons 3 and 4 of the mouse Brca2 gene occurring specifically in mammary epithelial cells of conditional female mutants carrying a combination of loxP-modified and null Brca2 alleles resulted in a high incidence (77%) of breast tumors that were often palpable and developed in one or more glands after long latency (time for median tumor-free survival of approximately 1.4 years; total of 40 tumors in 20 animals). These invasive adenocarcinomas were histologically quite uniform, exhibiting predominantly a solid, nodular tumor pattern with very few variants, in striking contrast to the morphological heterogeneity of analogous Brca1-associated tumors. The karyotypes of tumor cells lacking Brca2 had various chromosomal aberrations and ranged from diploid to hypertetraploid, but this wide variability was incongruous with the histological appearance of carcinomas that was comparable between specimens. The implications of these observations in the context of models positing that Brca2 is involved in the maintenance of genomic stability are discussed.

Adenocarcinoma↗

Tumorigenesis in mice carrying a truncating Brca1 mutation.

We generated mouse mutants carrying in the Brca1 locus a modification (Brca1(tr)) that eliminates the C-terminal half of the protein product and obtained results indicating that, depending on genetic background, the missing BRCT and/or other domains are dispensable for survival, but essential for tumor suppression. Most of the apparently hypomorphic Brca1(tr/tr) mutants developed various tumors. Lymphomas were detected at all ages, whereas sarcomas and carcinomas, including breast cancer, appeared after a long latency. The mammary tumors showed striking variability in histopathological patterns suggesting stochastic engagement of tumorigenic pathways in their progression, to which the Brca1(tr/tr) mutation was apparently a late participant.

Animals↗