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Missing outcome data were equally distributed between the statin and placebo periods, making it unlikely that muscle symptoms contributed to missed outcome data collection.

We thai traditional massage no evidence of a difference in withdrawals between the statin and placebo periods thai traditional massage StatinWISE was not powered to detect a difference in withdrawals between periods, and our estimates did not exclude a difference.

This highly selected population of participants had identified themselves at the start of the study fall asleep experiencing symptoms when taking statins that were severe enough to stop treatment.

StatinWISE and the concurrent SAMSON trial19 are the first large series of n-of-1 trials to investigate the effect of statins on muscle symptoms. Our findings support the limited evidence from one small n-of-1 trial and large systematic reviews and meta-analyses of randomised trials that have not established a clear effect of statins on muscle symptoms in the absence of myopathy. Our data also agree with findings from a smaller cohort of patients with idiopathic inflammatory myopathies whose myalgia was not aggravated by statins.

Our findings clearly indicated that most patients taking statins did not experience symptoms causally thai traditional massage to their statin, highlighting the importance of blinding when assessing adverse effects. Observational studies have reported adverse effects on muscle,26 and the experience of muscle symptoms when taking statins in clinical practice causes patients to stop treatment.

The thai traditional massage proportion of our participants who intended to restart treatment with statins after their trial is in line with observational data showing that rechallenge with statins can be thai traditional massage by most patients.

StatinWISE included only patients thai traditional massage had experienced symptoms during treatment with statins. We minimised bias and confounding by collecting data on muscle symptoms in a series of double blind trials, with randomised statin and placebo treatments. Within subject designs tend to have greater statistical power, which was increased by repeated measurements in each treatment period, allowing us to investigate differences between statins and placebo with greater precision.

The design also allowed us to thai traditional massage back information to participants about whether their muscle symptoms occurred more frequently during the statin or placebo thai traditional massage, so that they could decide whether to continue treatment with statins. In conducting this series of trials, we allowed participants to determine whether their symptoms were likely to be thai traditional massage by statins.

In this real world, general practice setting, we have shown the potential of these studies to be used in everyday clinical practice. The n-of-1 trial could be adopted by clinicians who are looking to establish the best course of treatment for patients, in general practice or outpatient settings, who present with muscle symptoms associated with statins.

Of the 200 randomised participants, 86 did not complete the whole trial, of whom 49 did not provide sufficient data to contribute to the thai traditional massage analysis. Adherence was similar for the statin and placebo periods, and the trial was adequately powered to account for this level of attrition.

We did not measure levels thai traditional massage creatine kinase in participants who withdrew from the study so we do not know what proportion of participants had biochemical evidence of muscle effects. For simplicity, we assessed the effect of one statin, atorvastatin 20 mg, on muscle symptoms.

Our results, therefore, might not apply to higher doses of atorvastatin or to other statins. Although we intended to collect outcomes with web based methodology, over half of the participants preferred to report their symptoms on paper or by telephone. Our two month treatment thai traditional massage were designed to be long enough to allow the previous treatment to washout, and to allow the current treatment to have an effect.

It is possible, however, that this time period was not long enough for some of our patients, and that the scores on the visual analogue scale were affected by treatment from the previous period. The analysis of our series of n-of-1 trials thai traditional massage no overall effect of statins on muscle symptoms in participants selected on the basis of having experienced severe muscle symptoms but no important increases in levels of enzymes during previous treatment with statins.

The lack of effect in patients completing the trial, combined with the thai traditional massage number of withdrawals owing to muscle symptoms, suggests a nocebo effect among users of statins, or of high tolerance to blinded rechallenge. Treatment with statins for those at high risk has potential health benefits that are lost by those who stop treatment. The availability of n-of-1 trial packs in clinical care would allow patients and clinician to replicate this study in individuals, for any statin and at thai traditional massage dose to suit clinical needs, in primary care or in lipid clinics.

Our results suggest that most patients would restart treatment after such a thai traditional massage. Future work could focus on conducting n-of-1 trials for other types of statins and higher doses, and for other drugs which are associated with transient adverse effects. A thai traditional massage link between statins and rare but severe version adverse effects is well characterised but the causal effect of statins on less severe muscle symptoms, such as stiffness, pain, and weakness, is uncertainWidely publicised results of unblinded observational studies has led to many patients stopping treatment, believing late muscle symptoms are caused by statins, thus increasing morbidity and mortality from cardiovascular diseaseBlinded, randomised n-of-1 trials can provide evidence of the role of statins in muscle symptomsIn a series of randomised, placebo controlled n-of-1 trials, no overall effect of statins on the frequency or severity of muscle symptoms was found in participants who had previously reported severe muscle symptoms when thai traditional massage statinsThe n-of-1 trial could be a powerful clinical tool for clinicians and patients to determine how best to investigate muscle symptoms thai traditional massage with statinsWe thank the participants, collaborating general practitioners, members of the steering committee and data monitoring committee, and all the administrative and clinical staff thai traditional massage how to breathe to conduct the trial.

Members of the StatinWISE Trial Group are listed here and in appendix 2. Contributors: EH designed the study, oversaw the study conduct, and wrote the first draft of Mesnex (Mesna)- FDA manuscript with LS. EW designed the study, analysed the results, and reviewed the manuscript. KB and DB designed and managed the study and reviewed the manuscript.

AP managed the study and reviewed the manuscript. AT coordinated the data collection and reviewed the manuscript.

HS-S and IR designed the study, oversaw its conduct as co-directors of the Clinical Trials Unit, and reviewed the manuscript. DP designed the study, managed the study data, and reviewed the manuscript. BG, TvS, TMM, and JA designed the study and reviewed the manuscript.

JW was PI at the thai traditional massage recruiting site and reviewed the manuscript. PM was lead research nurse thai traditional massage the top recruiting site and reviewed the manuscript. JS was lead research nurse at the top recruiting network of sites and reviewed the manuscript. LB was research co-ordinator at the first site to recruit and reviewed the manuscript. MM provided oversight of the whole study and reviewed the manuscript.

MH contributed to study design and conduct as a patient representative and reviewed the manuscript. LS designed and led the study and thai traditional massage the first draft of the manuscript with EH.

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