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The Cochrane Database of Systematic... May 2024Sickle cell disease (SCD) refers to a group of genetic disorders characterized by the presence of an abnormal haemoglobin molecule called haemoglobin S (HbS). When... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sickle cell disease (SCD) refers to a group of genetic disorders characterized by the presence of an abnormal haemoglobin molecule called haemoglobin S (HbS). When subjected to oxidative stress from low oxygen concentrations, HbS molecules form rigid polymers, giving the red cell the typical sickle shape. Antioxidants have been shown to reduce oxidative stress and improve outcomes in other diseases associated with oxidative stress. Therefore, it is important to review and synthesize the available evidence on the effect of antioxidants on the clinical outcomes of people with SCD.
OBJECTIVES
To assess the effectiveness and safety of antioxidant supplementation for improving health outcomes in people with SCD.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 15 August 2023.
SELECTION CRITERIA
We included randomized and quasi-randomized controlled trials comparing antioxidant supplementation to placebo, other antioxidants, or different doses of antioxidants, in people with SCD.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed the risk of bias and certainty of the evidence, and reported according to Cochrane methodological procedures.
MAIN RESULTS
The review included 1609 participants in 26 studies, with 17 comparisons. We rated 13 studies as having a high risk of bias overall, and 13 studies as having an unclear risk of bias overall due to study limitations. We used GRADE to rate the certainty of evidence. Only eight studies reported on our important outcomes at six months. Vitamin C (1400 mg) plus vitamin E (800 mg) versus placebo Based on evidence from one study in 83 participants, vitamin C (1400 mg) plus vitamin E (800 mg) may not be better than placebo at reducing the frequency of crisis (risk ratio (RR) 1.18, 95% confidence interval (CI) 0.64 to 2.18), the severity of pain (RR 1.33, 95% CI 0.40 to 4.37), or adverse effects (AE), of which the most common were headache, nausea, fatigue, diarrhoea, and epigastric pain (RR 0.56, 95% CI 0.31 to 1.00). Vitamin C plus vitamin E may increase the risk of SCD-related complications (acute chest syndrome: RR 2.66, 95% CI 0.77 to 9.13; 1 study, 83 participants), and increase haemoglobin level (median (interquartile range) 90 (81 to 96) g/L versus 93.5 (84 to 105) g/L) (1 study, 83 participants) compared to placebo. However, the evidence for all the above effects is very uncertain. The study did not report on quality of life (QoL) of participants and their caregivers, nor on frequency of hospitalization. Zinc versus placebo Zinc may not be better than placebo at reducing the frequency of crisis at six months (rate ratio 0.62, 95% CI 0.17 to 2.29; 1 study, 36 participants; low-certainty evidence). We are uncertain whether zinc is better than placebo at improving sickle cell-related complications (complete healing of leg ulcers at six months: RR 2.00, 95% CI 0.60 to 6.72; 1 study, 34 participants; very low-certainty evidence). Zinc may be better than placebo at increasing haemoglobin level (g/dL) (MD 1.26, 95% CI 0.44 to 1.26; 1 study, 36 participants; low-certainty evidence). The study did not report on severity of pain, QoL, AE, and frequency of hospitalization. N-acetylcysteine versus placebo N-acetylcysteine (NAC) 1200 mg may not be better than placebo at reducing the frequency of crisis in SCD, reported as pain days (rate ratio 0.99 days, 95% CI 0.53 to 1.84; 1 study, 96 participants; low-certainty evidence). Low-certainty evidence from one study (96 participants) suggests NAC (1200 mg) may not be better than placebo at reducing the severity of pain (MD 0.17, 95% CI -0.53 to 0.87). Compared to placebo, NAC (1200 mg) may not be better at improving physical QoL (MD -1.80, 95% CI -5.01 to 1.41) and mental QoL (MD 2.00, 95% CI -1.45 to 5.45; very low-certainty evidence), reducing the risk of adverse effects (gastrointestinal complaints, pruritus, or rash) (RR 0.92, 95% CI 0.75 to 1.14; low-certainty evidence), reducing the frequency of hospitalizations (rate ratio 0.98, 95% CI 0.41 to 2.38; low-certainty evidence), and sickle cell-related complications (RR 5.00, 95% CI 0.25 to 101.48; very low-certainty evidence), or increasing haemoglobin level (MD -0.18 g/dL, 95% CI -0.40 to 0.04; low-certainty evidence). L-arginine versus placebo L-arginine may not be better than placebo at reducing the frequency of crisis (monthly pain) (RR 0.71, 95% CI 0.26 to 1.95; 1 study, 50 participants; low-certainty evidence). However, L-arginine may be better than placebo at reducing the severity of pain (MD -1.41, 95% CI -1.65 to -1.18; 2 studies, 125 participants; low-certainty evidence). One participant allocated to L-arginine developed hives during infusion of L-arginine, another experienced acute clinical deterioration, and a participant in the placebo group had clinically relevant increases in liver function enzymes. The evidence is very uncertain whether L-arginine is better at reducing the mean number of days in hospital compared to placebo (MD -0.85 days, 95% CI -1.87 to 0.17; 2 studies, 125 participants; very low-certainty evidence). Also, L-arginine may not be better than placebo at increasing haemoglobin level (MD 0.4 g/dL, 95% CI -0.50 to 1.3; 2 studies, 106 participants; low-certainty evidence). No study in this comparison reported on QoL and sickle cell-related complications. Omega-3 versus placebo Very low-certainty evidence shows no evidence of a difference in the risk of adverse effects of omega-3 compared to placebo (RR 1.05, 95% CI 0.74 to 1.48; 1 study, 67 participants). Very low-certainty evidence suggests that omega-3 may not be better than placebo at increasing haemoglobin level (MD 0.36 g/L, 95% CI -0.21 to 0.93; 1 study, 67 participants). The study did not report on frequency of crisis, severity of pain, QoL, frequency of hospitalization, and sickle cell-related complications.
AUTHORS' CONCLUSIONS
There was inconsistent evidence on all outcomes to draw conclusions on the beneficial and harmful effects of antioxidants. However, L-arginine may be better than placebo at reducing the severity of pain at six months, and zinc may be better than placebo at increasing haemoglobin level. We are uncertain whether other antioxidants are beneficial for SCD. Larger studies conducted on each comparison would reduce the current uncertainties.
Topics: Humans; Anemia, Sickle Cell; Antioxidants; Ascorbic Acid; Bias; Dietary Supplements; Oxidative Stress; Placebos; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38775255
DOI: 10.1002/14651858.CD013590.pub2 -
Tidsskrift For Den Norske Laegeforening... Nov 2017
Topics: Acupuncture Therapy; Humans; Placebos
PubMed: 29181912
DOI: 10.4045/tidsskr.17.0478 -
The Journal of Pediatrics Feb 2017To assess parental attitudes regarding placebo use in pediatric randomized controlled trials and clinical care.
OBJECTIVE
To assess parental attitudes regarding placebo use in pediatric randomized controlled trials and clinical care.
STUDY DESIGN
Parents with children under age 18 years living in the US completed and submitted an online survey between September and November 2014.
RESULTS
Among all 1300 participants, 1000 (76.9%; 538 mothers and 462 fathers) met the study inclusion criteria. The majority of surveyed parents considered the use of placebos acceptable in some pediatric care situations (86%) and some pediatric trials (91.5%), whereas only 5.7% of parents found the use of placebos in children always unacceptable. The clinical use of placebo was considered acceptable by a majority of parents for only 7 (mostly psychological) of the 17 conditions presented. Respondents' judgment about acceptability was influenced by the doctors' opinions about the therapeutic benefits of placebo treatment, the conditions for pediatric placebo use, transparency, safety, and purity of placebos.
CONCLUSION
Most surveyed parents accepted the idea of using placebos in pediatric trials and within the clinic for some conditions without the practice of deception and with the creation of guidelines for ethical and safe use. This study suggests a need to reconsider pediatric trial design and clinical therapy in the light of generally positive parental support of appropriate placebo use.
Topics: Adolescent; Adult; Attitude; Child; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Parents; Placebos; Surveys and Questionnaires; United States; Young Adult
PubMed: 27863847
DOI: 10.1016/j.jpeds.2016.10.018 -
International Review of Neurobiology 2018The present paper reviews how language and communication are used to describe placebo phenomena in medicine, with particular reference at key points to the question of... (Review)
Review
The present paper reviews how language and communication are used to describe placebo phenomena in medicine, with particular reference at key points to the question of pain. Selected aspects of placebo language are submitted to lexical, grammatical and semantic analysis. We distinguish three uses of placebo, with three semantic components: "pleasing," inert medication or procedure, and what is often called "deception." The three uses of placebo are: Placebo-treatment, which combines all three semantic components: "pleasing" patients with inert treatments, and possibly with "deception." Placebo-trial, which refers to the closely defined inert control in Randomized Controlled Trials. Placebo-rapport, which covers all aspects of the health care encounter, excluding therapeutic interventions, but including psychosocial factors which can have a beneficial effect on the patient. Three key conclusions emerge from this analysis. First, the "deception" connotation of placebo found in placebo-treatment can contaminate the use of placebo-trial and especially placebo-rapport. Second, the enlarged "pleasing" framework of placebo-rapport, which includes the benefits of quality appropriate and helpful medical care, forces us to ask whether placebo-trial in Randomized Controlled Trials has in fact been a neutral baseline control. Biopsychosocial and other factors in placebo-rapport may have influenced the outcomes of many trials in medicine and pharmacology. And third, extending placebo-rapport to embrace all aspects of clinical care (except specific medication or procedural interventions) and psychosocial factors of the health care encounter engages patient beliefs, mindsets and interpersonal dynamics, as well as values and contextual and cultural issues. These take placebo-rapport substantially beyond what is currently seen as its identity and modes of operation.
Topics: Humans; Linguistics; Placebo Effect; Placebos; Psychology; Randomized Controlled Trials as Topic; Semantics
PubMed: 30146059
DOI: 10.1016/bs.irn.2018.07.032 -
Pain Aug 2016Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with... (Review)
Review
Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22 studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Provided that nondisclosure is preauthorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated.
Topics: Analgesics; Animals; Humans; Pain; Pain Management; Placebos; Treatment Outcome
PubMed: 27023425
DOI: 10.1097/j.pain.0000000000000566 -
International Review of Neurobiology 2020Throughout the history of medicine, multiple conceptions of "placebo" and "placebo effect" have often co-existed across different domains, and today the meaning of these... (Review)
Review
Throughout the history of medicine, multiple conceptions of "placebo" and "placebo effect" have often co-existed across different domains, and today the meaning of these concepts is still disputed. Against this background, this chapter provides a succinct account of the key events in the history of the concepts of "placebo," "placebo control," and "placebo effect." The first section reconstructs the etymology of the term "placebo" and its first introduction in medicine. The next sections provide an account of how placebos have been employed in both medical practice and scientific research in modern medicine. Later sections trace the emergence of the concepts of "placebo control" and "placebo effect" in the first half of the 20th century, from the first empirical studies investigating the effects of placebos up to the publication of Beecher's landmark article "The Powerful Placebo." Finally, the last two sections review the varieties of randomized, placebo-controlled trials (RCTs) in the second half of the 20th century, and the subsequent wave of empirical studies that, starting from the 1970s, have investigated the psychological, pharmacological and neurobiological mechanisms of placebo effects.
Topics: Biomedical Research; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Placebo Effect; Placebos; Randomized Controlled Trials as Topic
PubMed: 32563292
DOI: 10.1016/bs.irn.2020.03.028 -
The Cochrane Database of Systematic... Apr 2021Dietary supplements with ginseng, or ginseng alone, are widely used for a broad range of conditions, including erectile dysfunction. Ginseng is particularly popular in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dietary supplements with ginseng, or ginseng alone, are widely used for a broad range of conditions, including erectile dysfunction. Ginseng is particularly popular in Asian countries. Individual studies assessing its effects are mostly small, of uneven methodological quality and have unclear results.
OBJECTIVES
To assess the effects of ginseng on erectile dysfunction.
SEARCH METHODS
We conducted systematic searches on multiple electronic databases, including CENTRAL, MEDLINE, Embase, CINAHL, AMED, and loco-regional databases of east Asia, from their inceptions to 30 January 2021 without restrictions on language and publication status. Handsearches included conference proceedings.
SELECTION CRITERIA
We included randomized or quasi-randomized controlled trials that evaluated the use of any type of ginseng as a treatment for erectile dysfunction compared to placebo or conventional treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently classified studies and three authors independently extracted data and assessed risk of bias in the included studies. We rated the certainty of evidence according to the GRADE approach.
MAIN RESULTS
We included nine studies with 587 men with mild to moderate erectile dysfunction, aged from 20 to 70 years old. The studies all compared ginseng to placebo. We found only short-term follow-up data (up to 12 weeks). Primary outcomes Ginseng appears to have a trivial effect on erectile dysfunction when compared to placebo based on the Erectile Function Domain of the International Index of Erectile Function (IIEF)-15 instrument (scale: 1 to 30, higher scores imply better function; mean difference [MD] 3.52, 95% confidence interval [CI] 1.79 to 5.25; I² = 0%; 3 studies; low certainty evidence) assuming a minimal clinically important difference (MCID) of 4. Ginseng probably also has a trivial effect on erectile function when compared to placebo based on the IIEF-5 instrument (scale: 1 to 25, higher scores imply better function; MD 2.39, 95% CI 0.89 to 3.88; I² = 0%; 3 studies; moderate certainty evidence) assuming a MCID of 5. Ginseng may have little to no effect on adverse events compared to placebo (risk ratio [RR] 1.45, 95% CI 0.69 to 3.03; I² = 0%; 7 studies; low certainty evidence). Based on 86 adverse events per 1000 men in the placebo group, this would correspond to 39 more adverse events per 1000 (95% CI 27 fewer to 174 more). Secondary outcomes Ginseng may improve men's self-reported ability to have intercourse (RR 2.55, 95% CI 1.76 to 3.69; I² = 23%; 6 studies; low certainty evidence). Based on 207 per 1000 men self-reporting the ability to have intercourse in the placebo group, this would correspond to 321 more men (95% CI 158 more to 558 more) per 1000 self-reporting the ability to have intercourse. Ginseng may have a trivial effect on men's satisfaction with intercourse based on the Intercourse Satisfaction Domain of the IIEF-15 (scale: 0 to 15, higher scores imply greater satisfaction; MD 1.19, 95% CI 0.41 to 1.97; I²=0%; 3 studies; low certainty evidence) based on a MCID of 25% improvement from baseline. It may also have a trivial effect on men's satisfaction with intercourse based on item 5 of the IIEF-5 (scale: 0 to 5, higher scores imply more satisfaction; MD 0.60, 95% CI 0.02 to 1.18; 1 study; low certainty evidence) based on a MCID of 25% improvement from baseline. No study reported quality of life as an outcome. We found no trial evidence to inform comparisons to other treatments for erectile dysfunction, such as phosphodiesterase-5 inhibitors. We were unable to conduct any predefined subgroup analyses.
AUTHORS' CONCLUSIONS
Based on mostly low certainty evidence, ginseng may only have trivial effects on erectile function or satisfaction with intercourse compared to placebo when assessed using validated instruments. Ginseng may improve men's self-reported ability to have intercourse. It may have little to no effect on adverse events. We found no trial evidence comparing ginseng to other agents with a more established role in treating erectile dysfunction, such as phosphodiesterase-5 inhibitors.
Topics: Adult; Aged; Coitus; Confidence Intervals; Erectile Dysfunction; Humans; Male; Middle Aged; Panax; Patient Satisfaction; Phytotherapy; Placebos; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33871063
DOI: 10.1002/14651858.CD012654.pub2 -
International Review of Neurobiology 2018Treatment-related expectations are important predictors for placebo effects in various medical conditions. They are formed by verbal and nonverbal cues during the... (Review)
Review
Treatment-related expectations are important predictors for placebo effects in various medical conditions. They are formed by verbal and nonverbal cues during the administration of treatments, such as verbal suggestions, conscious and unconscious associations with previous treatments, characteristics of patients and health-care providers as well as perceptual characteristics of the treatment. This review provides an overview of studies that aimed to elucidate the impact of treatment characteristics on expectations and placebo effects. Results show that high price, brand label, the use of invasive placebos and high placebo dose increase the expectations toward the beneficial effect of a placebo treatment, which in turn boost the placebo effect. Neuroimaging studies provide first insights into the neurobiological mechanisms underlying these differential placebo effects.
Topics: Attitude; Color Perception; Humans; Placebo Effect; Placebos
PubMed: 30146054
DOI: 10.1016/bs.irn.2018.07.014 -
The Cochrane Database of Systematic... Nov 2020This is an update of a Cochrane Review, first published in 2005. Hemifacial spasm (HFS) is characterised by unilateral, involuntary contractions of the muscles...
BACKGROUND
This is an update of a Cochrane Review, first published in 2005. Hemifacial spasm (HFS) is characterised by unilateral, involuntary contractions of the muscles innervated by the facial nerve. It is a chronic disorder, and spontaneous recovery is very rare. The two treatments routinely available are microvascular decompression and intramuscular injections with botulinum toxin type A (BtA).
OBJECTIVES
To compare the efficacy, safety, and tolerability of BtA versus placebo in people with HFS.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, reference lists of articles, and conference proceedings in July 2020. We ran the electronic database search, with no language restrictions, in July 2020.
SELECTION CRITERIA
Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with HFS.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed records. We planned to select included studies, extract data using a paper pro forma, and evaluate the risk of bias. We resolved disagreements by consensus, or by consulting a third review author. We planned to perform meta-analyses. The primary efficacy outcome was HFS-specific improvement. The primary safety outcome was the proportion of participants with any adverse event.
MAIN RESULTS
We found no parallel-group randomised controlled trials comparing BtA and placebo in HFS.
AUTHORS' CONCLUSIONS
We did not find any randomised trials that evaluated the efficacy and safety of botulinum toxin type A in people with hemifacial spasm, so we are unable to draw any conclusions. Observational data show a strong association between BtA treatment and symptom improvement, and a favourable safety profile. While it is unlikely that future placebo-controlled RCTs will evaluate absolute efficacy and safety, they should address relevant questions for both people with HFS (such as long-term effects, quality of life, and other patient-reported outcomes), and clinicians (such as relative effectiveness of different BtA formulations and schemes of treatment) to better guide clinical practice.).
Topics: Botulinum Toxins, Type A; Hemifacial Spasm; Humans; Neuromuscular Agents; Placebos
PubMed: 33211908
DOI: 10.1002/14651858.CD004899.pub3 -
The Cochrane Database of Systematic... Jul 2021Dentinal hypersensitivity is characterized by short, sharp pain from exposed dentine that occurs in response to external stimuli such as cold, heat, osmotic, tactile or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dentinal hypersensitivity is characterized by short, sharp pain from exposed dentine that occurs in response to external stimuli such as cold, heat, osmotic, tactile or chemicals, and cannot be explained by any other form of dental defect or pathology. Laser therapy has become a commonly used intervention and might be effective for dentinal hypersensitivity.
OBJECTIVES
To assess the effects of in-office employed lasers versus placebo laser, placebo agents or no treatment for relieving pain of dentinal hypersensitivity.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 October 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2020, Issue 9), MEDLINE Ovid (1946 to 20 October 2020), Embase Ovid (1980 to 20 October 2020), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 20 October 2020), and LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; from 1982 to 20 October 2020). Conference proceedings were searched via the ISI Web of Science and ZETOC, and OpenGrey was searched for grey literature. The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
Randomized controlled trials (RCTs) in which in-office lasers were compared to placebo or no treatment on patients aged above 12 years with tooth hypersensitivity.
DATA COLLECTION AND ANALYSIS
Two review authors independently and in duplicate screened the search results, extracted data, and assessed the risk of bias of the included studies. Disagreement was resolved by discussion. For continuous outcomes, we used mean differences (MD) and 95% confidence intervals (CI). We conducted meta-analyses only with studies of similar comparisons reporting the same outcome measures. We assessed the overall certainty of the evidence using GRADE.
MAIN RESULTS
We included a total of 23 studies with 936 participants and 2296 teeth. We assessed five studies at overall low risk of bias, 13 at unclear, and five at high risk of bias. 17 studies contributed data to the meta-analyses. We divided the studies into six subgroups based on the type of laser and the primary outcome measure. We assessed the change in intensity of pain using quantitative pain scale (visual analogue scale (VAS) of 0 to 10 (no pain to worst possible pain)) when tested through air blast and tactile stimuli in three categories of short (0 to 24 hours), medium (more than 24 hours to 2 months), and long term (more than 2 months). Results demonstrated that compared to placebo or no treatment the application of all types of lasers combined may reduce pain intensity when tested through air blast stimuli at short term (MD -2.24, 95% CI -3.55 to -0.93; P = 0.0008; 13 studies, 978 teeth; low-certainty evidence), medium term (MD -2.46, 95% CI -3.57 to -1.35; P < 0.0001; 11 studies, 1007 teeth; very low-certainty evidence), and long term (MD -2.60, 95% CI -4.47 to -0.73; P = 0.006; 5 studies, 564 teeth; very low-certainty evidence). Similarly, compared to placebo or no treatment the application of all types of lasers combined may reduce pain intensity when tested through tactile stimuli at short term (MD -0.67, 95% CI -1.31 to -0.03; P = 0.04; 8 studies, 506 teeth; low-certainty evidence) and medium term (MD -1.73, 95% CI -3.17 to -0.30; P = 0.02; 9 studies, 591 teeth; very low-certainty evidence). However, there was insufficient evidence of a difference in pain intensity for all types of lasers when tested through tactile stimuli in the long term (MD -3.52, 95% CI -10.37 to 3.33; P = 0.31; 2 studies, 184 teeth; very low-certainty evidence). Most included studies assessed adverse events and reported that no obvious adverse events were observed during the trials. No studies investigated the impact of laser treatment on participants' quality of life.
AUTHORS' CONCLUSIONS
Limited and uncertain evidence from meta-analyses suggests that the application of laser overall may improve pain intensity when tested through air blast or tactile stimuli at short, medium, or long term when compared to placebo/no treatment. Overall, laser therapy appears to be safe. Future studies including well-designed double-blinded RCTs are necessary to further investigate the clinical efficacy of lasers as well as their cost-effectiveness.
Topics: Bias; Dentin Sensitivity; Humans; Laser Therapy; Pain Measurement; Placebos; Randomized Controlled Trials as Topic
PubMed: 34255856
DOI: 10.1002/14651858.CD009434.pub2