BACKGROUND: Atherosclerotic cardiovascular diseases (ACVDs), a condition characterised by lipid accumulation in arterial walls, which is often exacerbated by chronic inflammation disorders, is the major cause of mortality and morbidity worldwide. Colchicine, with its first medicinal use in ancient Egypt, is an inexpensive drug with anti-inflammatory properties. However, its role in primary prevention of ACVDs in the general population remains unknown. OBJECTIVES: To assess the clinical benefits and harms of colchicine as primary prevention of cardiovascular outcomes in the general population. SEARCH METHODS: We searched the Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, Web of Science, and LILACS. We searched ClinicalTrials.gov and WHO ICTRP for ongoing and unpublished studies. We also scanned the reference lists of relevant included studies, reviews, meta-analyses, and health technology reports to identify additional studies. There were no limitations on language, date of publication, or study setting. The search results were updated on 31 May 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs) in any setting, recruiting adults without pre-existing cardiovascular disease. We included trials that compared colchicine versus placebo, non-steroidal anti-inflammatory drugs, corticosteroids, immunomodulating drugs, or usual care. Our primary outcomes were all-cause mortality, non-fatal myocardial infarction, stroke, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors independently selected studies, extracted data, and performed risk of bias and GRADE assessments. MAIN RESULTS: We identified 15 RCTs (1721 participants randomised; 1412 participants analysed) with follow-up periods ranging from 4 to 728 weeks. The intervention was oral colchicine compared with placebo, immunomodulating drugs, or usual care or no treatment. Due to biases and imprecision, the evidence was very uncertain for all outcomes. All trials but one had a high risk of bias. Five out of seven meta-analyses included fewer than six trials (71.4%). The objectives of the review were to assess cardiovascular outcomes in the general population, but many of the included trials focused on liver disease. Colchicine compared to placebo Colchicine may reduce all-cause mortality compared to placebo in primary prevention, but the evidence is very uncertain (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.51 to 0.91; 6 studies, 463 participants; very low-certainty evidence; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 6 to 67). Colchicine may result in little to no difference in non-fatal myocardial infarction, but the evidence is very uncertain (RR 0.87, 95% CI 0.41 to 1.82; 1 study, 100 participants; very low-certainty evidence). Colchicine may not reduce the incidence of stroke, but the evidence is very uncertain (RR 2.43, 95% CI 0.67 to 8.86; 1 study, 100 participants; very low-certainty evidence). Regarding adverse events, colchicine may increase the incidence of diarrhoea (RR 3.99, 95% CI 1.44 to 11.06; 8 studies, 605 participants; very low-certainty evidence; number needed to treat for an additional harmful outcome (NNTH) 10, 95% CI 6 to 17), and may have little to no effect on neurological outcomes such as seizure or mental confusion (RR 0.72, 95% CI 0.31 to 1.66; 2 studies, 155 participants; very low-certainty evidence), but the evidence is very uncertain. The effect of colchicine on cardiovascular mortality is also very uncertain (RR 1.27, 95% CI 0.03 to 62.43; 2 studies, 160 participants; very low-certainty evidence). Colchicine may not reduce post-cardiac procedure atrial fibrillation, but the evidence is very uncertain (RR 0.74, 95% CI 0.25 to 2.19; 1 study, 100 participants). We found no trials reporting on pericardial effusion, peripheral artery disease, heart failure, or unstable angina. Colchicine compared to methotrexate (immunomodulating drug) Colchicine may result in little to no difference in all-cause mortality compared to methotrexate, but the evidence is very uncertain (RR 0.42, 95% CI 0.12 to 1.51; 1 study, 85 participants; very low-certainty evidence). We found no trials reporting other cardiovascular outcomes or adverse events for this comparison. Colchicine compared to usual care or no treatment The evidence is very uncertain about the effect of colchicine compared with usual care on all-cause mortality in primary prevention (RR 1.07, 95% CI 0.90 to 1.27; 2 studies, 729 participants; very low-certainty evidence). Regarding adverse events, colchicine may increase the incidence of diarrhoea compared to usual care, but the evidence is very uncertain (RR 3.32, 95% CI 1.56 to 7.03; 2 studies, 729 participants; very low-certainty evidence; NNTH 18, 95% CI 12 to 42). No trials reported other cardiovascular outcomes for this comparison. AUTHORS' CONCLUSIONS: This Cochrane review evaluated the clinical benefits and harms of using colchicine for the primary prevention of cardiovascular events in the general population. Comparisons were made against placebo, immunomodulating medications, or usual care or no treatment. However, the certainty of the evidence for the predefined outcomes was very low, highlighting the pressing need for high-quality, rigorous studies to ascertain colchicine's clinical impact definitively. We identified numerous biases and inaccuracies in the included studies, limiting their generalisability and precluding a conclusive determination of colchicine's efficacy in preventing cardiovascular events. The existing evidence regarding colchicine's potential cardiovascular benefits or harms for primary prevention is inconclusive owing to the limitations inherent in the current studies. More robust clinical trials are needed to bridge this evidence gap effectively.

• MeSH
• antiflogistika nesteroidní terapeutické užití   škodlivé účinky   MeSH
• antiflogistika terapeutické užití   škodlivé účinky   MeSH
• cévní mozková příhoda prevence a kontrola   mortalita   MeSH
• infarkt myokardu * prevence a kontrola   mortalita   epidemiologie   MeSH
• kardiovaskulární nemoci * prevence a kontrola   mortalita   MeSH
• kolchicin * terapeutické užití   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• příčina smrti MeSH
• primární prevence * metody   MeSH
• randomizované kontrolované studie jako téma * MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• antiflogistika MeSH
• kolchicin * MeSH

BACKGROUND: Atherosclerotic cardiovascular disease (ACVD) is worsened by chronic inflammatory diseases. Interleukin receptor antagonists (IL-RAs) and tumour necrosis factor-alpha (TNF) inhibitors have been studied to see if they can prevent cardiovascular events. OBJECTIVES: The purpose of this study was to assess the clinical benefits and harms of IL-RAs and TNF inhibitors in the primary and secondary prevention of ACVD. SEARCH METHODS: The Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, EBSCO CINAHL plus, and clinical trial registries for ongoing and unpublished studies were searched in February 2024. The reference lists of relevant studies, reviews, meta-analyses and health technology reports were searched to identify additional studies. No limitations on language, date of publication or study type were set. SELECTION CRITERIA: RCTs that recruited people with and without pre-existing ACVD, comparing IL-RAs or TNF inhibitors versus placebo or usual care, were selected. The primary outcomes considered were all-cause mortality, myocardial infarction, unstable angina, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors, working independently at each step, selected studies, extracted data, assessed the risk of bias and used GRADE to judge the certainty of evidence. MAIN RESULTS: We included 58 RCTs (22,053 participants; 21,308 analysed), comparing medication efficacy with placebo or usual care. Thirty-four trials focused on primary prevention and 24 on secondary prevention. The interventions included IL-1 RAs (anakinra, canakinumab), IL-6 RA (tocilizumab), TNF-inhibitors (etanercept, infliximab) compared with placebo or usual care. The certainty of evidence was low to very low due to biases and imprecision; all trials had a high risk of bias. Primary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality(RR 0.33, 95% CI 0.01 to 7.58, 1 trial), myocardial infarction (RR 0.71, 95% CI 0.04 to 12.48, I² = 39%, 2 trials), unstable angina (RR 0.24, 95% CI 0.03 to 2.11, I² = 0%, 2 trials), stroke (RR 2.42, 95% CI 0.12 to 50.15; 1 trial), adverse events (RR 0.85, 95% CI 0.59 to 1.22, I² = 54%, 3 trials), or infection (rate ratio 0.84, 95% 0.55 to 1.29, I² = 0%, 4 trials). Evidence is very uncertain about whether anakinra and cankinumab may reduce heart failure (RR 0.21, 95% CI 0.05 to 0.94, I² = 0%, 3 trials). Peripheral vascular disease (PVD) was not reported as an outcome. IL-6 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.68, 95% CI 0.12 to 3.74, I² = 30%, 3 trials), myocardial infarction (RR 0.27, 95% CI 0.04 to1.68, I² = 0%, 3 trials), heart failure (RR 1.02, 95% CI 0.11 to 9.63, I² = 0%, 2 trials), PVD (RR 2.94, 95% CI 0.12 to 71.47, 1 trial), stroke (RR 0.34, 95% CI 0.01 to 8.14, 1 trial), or any infection (rate ratio 1.10, 95% CI: 0.88 to 1.37, I2 = 18%, 5 trials). Adverse events may increase (RR 1.13, 95% CI 1.04 to 1.23, I² = 33%, 5 trials). No trial assessed unstable angina. TNF inhibitors The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.78, 95% CI 0.63 to 4.99, I² = 10%, 3 trials), myocardial infarction (RR 2.61, 95% CI 0.11 to 62.26, 1 trial), stroke (RR 0.46, 95% CI 0.08 to 2.80, I² = 0%; 3 trials), heart failure (RR 0.85, 95% CI 0.06 to 12.76, 1 trial). Adverse events may increase (RR 1.13, 95% CI 1.01 to 1.25, I² = 51%, 13 trials). No trial assessed unstable angina or PVD. Secondary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.94, 95% CI 0.84 to 1.06, I² = 0%, 8 trials), unstable angina (RR 0.88, 95% CI 0.65 to 1.19, I² = 0%, 3 trials), PVD (RR 0.85, 95% CI 0.19 to 3.73, I² = 38%, 3 trials), stroke (RR 0.94, 95% CI 0.74 to 1.2, I² = 0%; 7 trials), heart failure (RR 0.91, 95% 0.5 to 1.65, I² = 0%; 7 trials), or adverse events (RR 0.92, 95% CI 0.78 to 1.09, I² = 3%, 4 trials). There may be little to no difference between the groups in myocardial infarction (RR 0.88, 95% CI 0.0.75 to 1.04, I² = 0%, 6 trials). IL6-RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.09, 95% CI 0.61 to 1.96, I² = 0%, 2 trials), myocardial infarction (RR 0.46, 95% CI 0.07 to 3.04, I² = 45%, 3 trials), unstable angina (RR 0.33, 95% CI 0.01 to 8.02, 1 trial), stroke (RR 1.03, 95% CI 0.07 to 16.25, 1 trial), adverse events (RR 0.89, 95% CI 0.76 to 1.05, I² = 0%, 2 trials), or any infection (rate ratio 0.66, 95% CI 0.32 to 1.36, I² = 0%, 4 trials). No trial assessed PVD or heart failure. TNF inhibitors The evidence is very uncertain about the effect of the intervention on all-cause mortality (RR 1.16, 95% CI 0.69 to 1.95, I² = 47%, 5 trials), heart failure (RR 0.92, 95% 0.75 to 1.14, I² = 0%, 4 trials), or adverse events (RR 1.15, 95% CI 0.84 to 1.56, I² = 32%, 2 trials). No trial assessed myocardial infarction, unstable angina, PVD or stroke. Adverse events may be underestimated and benefits inflated due to inadequate reporting. AUTHORS' CONCLUSIONS: This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.

• MeSH
• ateroskleróza * prevence a kontrola   mortalita   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   škodlivé účinky   MeSH
• infarkt myokardu * prevence a kontrola   mortalita   MeSH
• lidé MeSH
• nestabilní angina pectoris prevence a kontrola   mortalita   MeSH
• příčina smrti MeSH
• primární prevence * metody   MeSH
• randomizované kontrolované studie jako téma MeSH
• receptory interleukinu-1 * antagonisté a inhibitory   MeSH
• sekundární prevence * metody   MeSH
• TNF-alfa * antagonisté a inhibitory   MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• canakinumab MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH
• receptory interleukinu-1 * MeSH
• TNF-alfa * MeSH
• tocilizumab MeSH Prohlížeč

BACKGROUND: Pain is prevalent during orthodontics, particularly during the early stages of treatment. To ensure patient comfort and compliance during treatment, the prevention or management of pain is of major importance. While pharmacological means are the first line of treatment for alleviation of orthodontic pain, a range of non-pharmacological approaches have been proposed recently as viable alternatives. OBJECTIVES: To assess the effects of non-pharmacological interventions to alleviate pain associated with orthodontic treatment. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 6 October 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 9), MEDLINE Ovid (1946 to 6 October 2016), Embase Ovid (1980 to 6 October 2016) and EThOS (to 6 October 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a non-pharmacological orthodontic pain intervention to a placebo, no intervention or another non-pharmacological pain intervention were eligible for inclusion. We included any type of orthodontic treatment but excluded trials involving the use of pre-emptive analgesia or pain relief following orthognathic (jaw) surgery or dental extractions in combination with orthodontic treatment. We excluded split-mouth trials (in which each participant receives two or more treatments, each to a separate section of the mouth) and cross-over trials. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed risk of bias and extracted data. We used the random-effects model and expressed results as mean differences (MD) with 95% confidence intervals (CI). We investigated heterogeneity with reference to both clinical and methodological factors. MAIN RESULTS: We included 14 RCTs that randomised 931 participants. Interventions assessed included: low-level laser therapy (LLLT) (4 studies); vibratory devices (5 studies); chewing adjuncts (3 studies); brain wave music or cognitive behavioural therapy (1 study) and post-treatment communication in the form of a text message (1 study). Twelve studies involved self-report assessment of pain on a continuous scale and two studies used questionnaires to assess the nature, intensity and location of pain.We combined data from two studies involving 118 participants, which provided low-quality evidence that LLLT reduced pain at 24 hours by 20.27 mm (95% CI -24.50 to -16.04, P < 0.001; I² = 0%). LLLT also appeared to reduce pain at six hours, three days and seven days.Results for the other comparisons assessed are inconclusive as the quality of the evidence was very low. Vibratory devices were assessed in five studies (272 participants), four of which were at high risk of bias and one unclear. Chewing adjuncts (chewing gum or a bite wafer) were evaluated in three studies (181 participants); two studies were at high risk of bias and one was unclear. Brain wave music and cognitive behavioural therapy were evaluated in one trial (36 participants) assessed at unclear risk of bias. Post-treatment text messaging (39 participants) was evaluated in one study assessed at high risk of bias.Adverse effects were not measured in any of the studies. AUTHORS' CONCLUSIONS: Overall, the results are inconclusive. Although available evidence suggests laser irradiation may help reduce pain during orthodontic treatment in the short term, this evidence is of low quality and therefore we cannot rely on the findings. Evidence for other non-pharmacological interventions is either very low quality or entirely lacking. Further prospective research is required to address the lack of reliable evidence concerning the effectiveness of a range of non-pharmacological interventions to manage orthodontic pain. Future studies should use prolonged follow-up and should measure costs and possible harms.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• kognitivně behaviorální terapie * MeSH
• kvalita života MeSH
• laserová terapie s nízkou intenzitou světla * MeSH
• lidé MeSH
• management bolesti metody   MeSH
• měření bolesti MeSH
• mladiství MeSH
• muzikoterapie * MeSH
• ortodoncie * MeSH
• posílání textových zpráv * MeSH
• randomizované kontrolované studie jako téma MeSH
• spokojenost pacientů MeSH
• vibrace terapeutické užití   MeSH
• žvýkačka * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• žvýkačka * MeSH