Spasticity is a common, debilitating symptom of multiple sclerosis (MS) with several treatment options including the cannabinoid-based treatment, nabiximols. The purpose of this review was to examine the existing clinical practice guidelines that direct the management of multiple-sclerosis-associated spasticity (MSS), to identify areas of similarity and divergence, and suggest where standardization and improvement may be obtained.
Published literature (PubMed), websites of relevant European Medical Associations and Health Technology Assessment bodies were systematically searched to identify guidelines describing the pharmacological management of MSS, focussing on European countries where nabiximols (Sativex® oromucosal spray) is approved. Sixteen publicly available guidelines were identified. Analysis was focused on, but not restricted to, the use of nabiximols in the wider context of the pharmacological treatment of MSS.
We believe that currently MSS is insufficiently treated and this would be improved if a clear and detailed set of guidelines were available and implemented in daily practice. We would welcome the update and amalgamation of the existing guidelines by an international panel, using an evidence-based approach, into a single guideline that is more detailed and standardized in its approach to the initiation, monitoring and optimization of anti-spasticity drugs.
People with multiple sclerosis often experience tight or stiff muscles and an inability to control those muscles. This is known as spasticity, which can have a devastating impact on a person’s ability to carry out their daily activities. In addition to physiotherapy, doctors can prescribe various medicines to improve spasticity; these are known as anti-spasticity treatments. Often, prescription choices are steered by guideline documents, written by medical experts. These documents contain important information such as when to prescribe, what to prescribe, how much to prescribe and how to measure how well the treatment is working. The purpose of this study was to examine whether the guidelines that guide the prescription of anti-spasticity treatments in people with multiple sclerosis in Europe, are fit for purpose for day-to-day medical practice. In particular, this article examines how the guidelines represent the newer cannabis-based treatment known as nabiximols, sold under the name Sativex oromucosal spray, which has become more widely available in many European countries over the last 10 years.

Several international guidelines for the acute treatment of moderate to severe unipolar depression recommend a first-line treatment with antidepressants (AD). This is based on the assumption that AD obviously outperform placebo, at least in the case of severe depression. The efficacy of AD for severe depression can only be definitely clarified with individual patient data, but corresponding studies have only been available recently. In this paper, we point out discrepancies between the content of guidelines and the scientific evidence by taking a closer look at the German S3-guidelines for the treatment of depression. Based on recent studies and a systematic review of studies using individual patient data, it turns out that AD are marginally superior to placebo in both moderate and severe depression. The clinical significance of this small drug-placebo-difference is questionable, even in the most severe forms of depression. In addition, the modest efficacy is likely an overestimation of the true efficacy due to systematic method biases. There is no related discussion in the S3-guidelines, despite substantial empirical evidence confirming these biases. In light of recent data and with their underlying biases, the recommendations in the S3-guidelines are in contradiction with the current evidence. The risk-benefit ratio of AD for severe depression may be similar to the one estimated for mild depression and thus could be unfavorable. Downgrading of the related grade of recommendation would be a logical consequence.

The 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published.
We performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1 000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke.
The cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84-0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73-0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79-0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes.
In a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors.

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The 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published.
We performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1,000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke.
The cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84-0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73-0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79-0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes.
In a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors.

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暂无摘要。