From the Diabetes Trials Unit (R.R.H., S.K.P., M.A.B.), the Division of Public Health and Primary Health Care (H.A.W.N.), and the National Institute of Health Re- search (NIHR) School for Primary Care Research (H.A.W.N.), Oxford Centre for Diabetes, Endocrinology, and Metabo- lism (R.R.H., S.K.P., M.A.B., D.R.M., H.A.W.N.); and the NIHR Oxford Bio- medical Research Centre (R.R.H., D.R.M., H.A.W.N.) — both in Oxford, United Kingdom. Address reprint requests to Dr. Holman at the Diabetes Trials Unit, Ox- ford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Head- ington, Oxford OX3 7LJ, United Kingdom, or at rury.holman@dtu.ox.ac.uk. Background During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose con- trol persisted and whether such therapy had a long-term effect on macrovascular outcomes. Methods Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned thera- pies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories. Results Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P = 0.04) and microvascular disease (24%, P = 0.001), and risk reductions for myocardial infarction (15%, P = 0.01) and death from any cause (13%, P = 0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-relat- ed end point (21%, P = 0.01), myocardial infarction (33%, P = 0.005), and death from any cause (27%, P = 0.002). Conclusions Despite an early loss of glycemic differences, a continued reduction in microvascu- lar risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN75451837.)

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10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes

Adequate reporting of randomized, controlled trials (RCTs) is necessary to allow accurate critical appraisal of the validity and applicability of the results. The CONSORT (Consolidated Standards of Reporting Trials) Statement, a 22-item checklist and flow diagram, is intended to address this problem by improving the reporting of RCTs. However, some specific issues that apply to trials of nonpharmacologic treatments (for example, surgery, technical interventions, devices, rehabilitation, psychotherapy, and behavioral intervention) are not specifically addressed in the CONSORT Statement. Furthermore, considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement. Therefore, the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments. A consensus meeting of 33 experts was organized in Paris, France, in February 2006, to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments. The participants extended 11 items from the CONSORT Statement, added 1 item, and developed a modified flow diagram. To allow adequate understanding and implementation of the CONSORT extension, the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting. This extension, in conjunction with the main CONSORT Statement and other CONSORT extensions, should help to improve the reporting of RCTs performed in this field.

/pdf/extending-the-consort-statement-to-randomized-trials-of-39t9d1gijb.pdf

Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration.

Publication and related bias in meta-analysis : power of statistical tests and prevalence in the literature

Background Although the benefits of public knowledge of physical diseases are widely accepted, knowledge about mental disorders (mental health literacy) has been comparatively neglected.

Aims To introduce the concept of mental health literacy to a wider audience, to bring together diverse research relevant to the topic and to identify gaps in the area.

Method A narrative review within a conceptual framework.

Results Many members of the public cannot recognise specific disorders or different types of psychological distress. They differ from mental health experts in their beliefs about the causes of mental disorders and the most effective treatments. Attitudes which hinder recognition and appropriate help-seeking are common. Much of the mental health information most readily available to the public is misleading. However, there is some evidence that mental health literacy can be improved.

Conclusions If the public's mental health literacy is not improved, this may hinder public acceptance of evidence-based mental health care. Also, many people with common mental disorders may be denied effective self-help and may not receive appropriate support from others in the community.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/5563369643662EC541F33D1DD307AD35/S000712500022730Xa.pdf/div-class-title-mental-health-literacy-div.pdf

Mental health literacy. Public knowledge and beliefs about mental disorders.

This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

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Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents)

Objective: To investigate if extracts of Hypericum perforatum (St John9s wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. Design: Systematic review and meta-analysis of trials revealed by searches. Trials: 23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. Main outcome measures: A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. Results: Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. Conclusion: There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed. Key messages There is evidence from randomised trials that such extracts are more effective than placebo for the treatment of depressive disorders, but it is not known whether they are more effective for certain disorders than others Current evidence is inadequate to establish whether hypericum is as effective as other antidepressants and if it has fewer side effects Additional trials should be conducted to compare hypericum with other antidepressants in well defined groups of patients; to investigate long term side effects; and to evaluate the relative efficacy of different preparations and doses

St John's wort for depression—an overview and meta-analysis of randomised clinical trials

ContextAcupuncture is widely used to prevent migraine attacks, but the available
evidence of its benefit is scarce.ObjectiveTo investigate the effectiveness of acupuncture compared with sham acupuncture
and with no acupuncture in patients with migraine.Design, Setting, and PatientsThree-group, randomized, controlled trial (April 2002-January 2003)
involving 302 patients (88% women), mean (SD) age of 43 (11) years, with migraine
headaches, based on International Headache Society criteria. Patients were
treated at 18 outpatient centers in Germany.InterventionsAcupuncture, sham acupuncture, or waiting list control. Acupuncture
and sham acupuncture were administered by specialized physicians and consisted
of 12 sessions per patient over 8 weeks. Patients completed headache diaries
from 4 weeks before to 12 weeks after randomization and from week 21 to 24
after randomization.Main Outcome MeasuresDifference in headache days of moderate or severe intensity between
the 4 weeks before and weeks 9 to 12 after randomization.ResultsBetween baseline and weeks 9 to 12, the mean (SD) number of days with
headache of moderate or severe intensity decreased by 2.2 (2.7) days from
a baseline of 5.2 (2.5) days in the acupuncture group compared with a decrease
to 2.2 (2.7) days from a baseline of 5.0 (2.4) days in the sham acupuncture
group, and by 0.8 (2.0) days from a baseline if 5.4 (3.0) days in the waiting
list group. No difference was detected between the acupuncture and the sham
acupuncture groups (0.0 days, 95% confidence interval, −0.7 to 0.7 days; P = .96) while there was a difference between
the acupuncture group compared with the waiting list group (1.4 days; 95%
confidence interval; 0.8-2.1 days; P<.001). The
proportion of responders (reduction in headache days by at least 50%) was
51% in the acupuncture group, 53% in the sham acupuncture group, and 15% in
the waiting list group.ConclusionAcupuncture was no more effective than sham acupuncture in reducing
migraine headaches although both interventions were more effective than a
waiting list control.

https://jamanetwork.com/journals/jama/articlepdf/200822/joc50026.pdf

Acupuncture for patients with migraine: a randomized controlled trial.

In a pooled analysis of four randomized controlled trials of acupuncture in patients with migraine, tension-type headache, chronic low back pain, and osteoarthritis of the knee we investigated the influence of expectations on clinical outcome. The 864 patients included in the analysis received either 12 sessions of acupuncture or minimal (i.e. sham) acupuncture (superficial needling of non-acupuncture points) over an 8 week period. Patients were asked at baseline whether they considered acupuncture to be an effective therapy in general and what they personally expected from the treatment. After three acupuncture sessions patients were asked how confident they were that they would benefit from the treatment strategy they were receiving. Patients were classified as responders if the respective main outcome measure improved by at least fifty percent. Both univariate and multivariate analyses adjusted for potential confounders (such as condition, intervention group, age, sex, duration of complaints, etc.) consistently showed a significant influence of attitudes and expectations on outcome. After completion of treatment, the odds ratio for response between patients considering acupuncture an effective or highly effective therapy and patients who were more sceptical was 1.67 (95% confidence interval 1.20-2.32). For personal expectations and confidence after the third session, odds ratios were 2.03 (1.26-3.26) and 2.35 (1.68-3.30), respectively. Results from the 6-month follow-up were similar. In conclusion, in our trials a significant association was shown between better improvement and higher outcome expectations.

The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain

Objective To investigate the effectiveness of acupuncture compared with minimal acupuncture and with no acupuncture in patients with tension-type headache.

Design Three armed randomised controlled multicentre trial.

Setting 28 outpatient centres in Germany.

Participants 270 patients (74% women, mean age 43 (SD 13) years) with episodic or chronic tension-type headache.

Interventions Acupuncture, minimal acupuncture (superficial needling at non-acupuncture points), or waiting list control. Acupuncture and minimal acupuncture were administered by specialised physicians and consisted of 12 sessions per patient over eight weeks.

Main outcome measure Difference in numbers of days with headache between the four weeks before randomisation and weeks 9-12 after randomisation, as recorded by participants in headache diaries.

Results The number of days with headache decreased by 7.2 (SD 6.5) days in the acupuncture group compared with 6.6 (SD 6.0) days in the minimal acupuncture group and 1.5 (SD 3.7) days in the waiting list group (difference: acupuncture v minimal acupuncture, 0.6 days, 95% confidence interval -1.5 to 2.6 days, P = 0.58; acupuncture v waiting list, 5.7 days, 3.9 to 7.5 days, P < 0.001). The proportion of responders (at least 50% reduction in days with headache) was 46% in the acupuncture group, 35% in the minimal acupuncture group, and 4% in the waiting list group.

Conclusions The acupuncture intervention investigated in this trial was more effective than no treatment but not significantly more effective than minimal acupuncture for the treatment of tension-type headache.

Trial registration number ISRCTN9737659.

/pdf/acupuncture-in-patients-with-tension-type-headache-49ryjkeazv.pdf

Wolfgang Weidenhammer

Papers

St John's wort for depression—an overview and meta-analysis of randomised clinical trials

Acupuncture for patients with migraine: a randomized controlled trial.

The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain

Acupuncture in patients with tension-type headache: randomised controlled trial

Prospective Investigation of Adverse Effects of Acupuncture in 97 733 Patients