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Public Health Aug 2023To determine the effect of recreational cannabis legalization (RCL) and/or recreational cannabis commercialization (RCC) on emergency department (ED) visits,... (Review)
Review
OBJECTIVE
To determine the effect of recreational cannabis legalization (RCL) and/or recreational cannabis commercialization (RCC) on emergency department (ED) visits, hospitalizations, and deaths due to substance use, injury, and mental health among those aged 11 years and older.
METHODS
A systematic review of six electronic databases up to February 1, 2023. Original, peer-reviewed articles with interrupted time series or before and after designs were included. Four independent reviewers screened articles and assessed risk of bias. Outcomes with 'critical' risk of bias were excluded. Protocol registered on PROSPERO (# CRD42021265183).
RESULTS
After screening and risk of bias assessment, 29 studies were included which examined ED visits or hospitalizations for cannabis use or alcohol (N = 10), opioid mortality (N = 3), motor vehicle fatalities or injury (N = 11), and intentional injury/mental health (N = 5). Rates or number of cannabis-related hospitalizations increased after RCL in Canada and the USA. Immediate increases in rates of cannabis-related ED visits were found after both RCL and RCC in Canada. Rates of traffic fatalities increased after RCL and RCC in certain jurisdictions in the USA.
CONCLUSIONS
RCL was associated with increased rates of cannabis-related hospitalizations. RCL and/or RCC was associated with increased rates of cannabis-related ED visits, consistently shown across sex and age groups. The effect on fatal motor vehicle incidents was mixed, with observed increases found after RCL and/or RCC. The effect of RCL or RCC on opioids, alcohol, intentional injury, and mental health is not clear. These results inform population health initiatives and international jurisdictions considering RCL implementation.
Topics: Humans; Cannabis; Mental Health; Carcinoma, Renal Cell; Substance-Related Disorders; Analgesics, Opioid; Legislation, Drug; Ethanol; Kidney Neoplasms
PubMed: 37429043
DOI: 10.1016/j.puhe.2023.06.012 -
Frontiers in Psychiatry 2022Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes...
Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant.
STUDY OBJECTIVES
Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.
METHODS
We conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval of each outcome.
RESULTS
Our search showed eight articles (five for suvorexant and three for lemborexant). Results of diary measures, rating scales, polysomnography results, treatment discontinuation, and adverse events were measured. All efficacy outcome measures favorably and significantly differed in the suvorexant compared to placebo. Safety profile did not differ significantly except for somnolence, excessive daytime sleepiness/sedation, fatigue, back pain, dry mouth, and abnormal dreams. Important adverse events including hallucinations, suicidal ideation/behavior and motor vehicle accidents did not differ between suvorexant and placebo. All the efficacy outcomes significantly differed between lemborexant 5 and lemborexant 10 compared to placebo. Somnolence rate for lemborexant 5 and lemborexant 10 and nightmare for lemborexant 10 were significantly higher than placebo.
CONCLUSION
The present meta-analysis reported that suvorexant and lemborexant are efficacious and safe agents for the patients with insomnia. Further data in patients with insomnia and various comorbid conditions are needed.
PubMed: 36578296
DOI: 10.3389/fpsyt.2022.1070522 -
CNS Neuroscience & Therapeutics Jul 2023Serpin is a superfamily of serine proteinase inhibitors. They have anticoagulative activities and immunoregulatory effects. The family has been widely studied in stroke... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Serpin is a superfamily of serine proteinase inhibitors. They have anticoagulative activities and immunoregulatory effects. The family has been widely studied in stroke patients and animal stroke models. However, results from clinical and preclinical studies are controversial. The systematic review and meta-analysis aimed to determine whether serpin activities are affected by stroke and whether members of the serpin family could be used in stroke treatment.
METHODS
Literature was systematically searched in six databases until September 5, 2022. In the included studies, 47 clinical studies (8276 subjects) reported concentrations of serpin proteins in stroke patients and healthy controls. In total, 41 preclinical studies (742 animals) reported neurological outcomes in animal models with serpin treatment and vehicle.
RESULTS
Meta-analysis of clinical studies showed that both ischemic (IS) and hemorrhagic stroke patients had higher thrombin-antithrombin complex (TAT) levels and lower antithrombin (AT) levels which were persistent in the acute and subacute phase of IS. Meta-analysis of preclinical studies reported the efficacy of serpins in treating stroke. C1-INH and FUT175 reduced brain infarct size and improved sensorimotor and motor behavior in a dose- and time-dependent manner in the MCAO models.
CONCLUSIONS
Our study confirmed the important roles serpin family proteins played in the onset, progression, and treatment of stroke. Among serpins, AT and TAT may be used as blood biomarkers in the early diagnosis of stroke. C1-INH and FUT175 could be potential medications for IS.
Topics: Animals; Serpins; Biomarkers; Models, Animal; Stroke
PubMed: 37017398
DOI: 10.1111/cns.14205 -
Journal of Pediatric Nursing 2019To determine the safety and efficacy of topical corticosteroid versus vehicle/moisturizer in children under 2 years old (<2 y). (Comparative Study)
Comparative Study Meta-Analysis
PROBLEM
To determine the safety and efficacy of topical corticosteroid versus vehicle/moisturizer in children under 2 years old (<2 y).
ELIGIBILITY CRITERIA
A systematic review and meta-analysis searching PubMed MEDLINE, Embase, Web of Science, Cochrane Database of Controlled Trials, Cochrane Database of Systematic Reviews, DARE, NHS Economic Evaluation, CINAHL, GREAT, and Clinicaltrials.gov. We selected randomized controlled trials (RCTs) comparing topical corticosteroids to vehicle/moisturizer and included children <2 y. Two authors extracted data.
SAMPLE
Only one study limited analyses to children <2 y, so our review included participants older than 2 years. Twelve RCTs were included with 2224 participants. Ten studies were industry-sponsored.
RESULTS
The proportion of responders to topical corticosteroid across studies was 0.65 (95% CI, 0.54-0.74), as compared to vehicle/moisturizer 0.32 (95% confidence interval (CI), 0.20-0.48). The proportion of adverse events were similar between groups (topical steroids 0.17 (95% CI, 0.08-0.33) vs. vehicle/moisturizer 0.12 (CI 0.02-0.42)). High heterogeneity in treatment response occurred across studies that could not be explained by potential moderators. Mild adrenal suppression occurred in 4 of 157 measured participants (3%) receiving topical corticosteroids. Limitations include the few RCTs on this topic, the inclusion of participants >2 y and outcome measures and reporting methods rarely met CONSORT guidelines.
CONCLUSIONS
Topical corticosteroids trended to being more effective and equally safe to vehicle/moisturizers, but generalizability is limited given the dearth of well-designed studies focused on children <2 y. Adverse events from vehicle/moisturizer may be greater than topical corticosteroid due to under treatment.
IMPLICATIONS
Further work is needed in this age group.
Topics: Administration, Topical; Adrenal Cortex Hormones; Child; Dermatitis, Atopic; Humans; Pharmaceutical Vehicles; Skin Cream
PubMed: 31026679
DOI: 10.1016/j.pedn.2019.03.018 -
World Neurosurgery Apr 2024Traumatic spinal cord injury (TSCI) is a debilitating neurological condition with significant long-term consequences on the mental health and well-being of affected... (Review)
Review
BACKGROUND
Traumatic spinal cord injury (TSCI) is a debilitating neurological condition with significant long-term consequences on the mental health and well-being of affected individuals. We aimed to investigate anxiety and depression in individuals with pediatric-onset TSCI.
METHODS
PubMed, Scopus, and Web of Science databases were searched from inception to December 20th, 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and studies were included according to the eligibility criteria.
RESULTS
A total of 1013 articles were screened, and 18 studies with 4234 individuals were included in the final review. Of these, 1613 individuals (38.1%) had paraplegia, whereas 1658 (39.2%) had tetraplegia. A total of 1831 participants (43.2%) had complete TSCI, whereas 1024 (24.2%) had incomplete TSCI. The most common etiology of TSCI with 1545 people (36.5%) was motor vehicle accidents. The youngest mean age at the time of injury was 5.92 ± 4.92 years, whereas the oldest was 14.6 ± 2.8 years. Patient Health Questionnaire-9 was the most common psychological assessment used in 9 studies (50.0%). Various risk factors, including pain in 4 studies (22.2%), reduced sleep quality, reduced functional independence, illicit drug use, incomplete injury, hospitalization, reduced quality of life, and duration of injury in 2 (11.1%) studies, each, were associated with elevated anxiety and depression.
CONCLUSIONS
Different biopsychosocial risk factors contribute to elevated rates of anxiety and depression among individuals with pediatric-onset TSCI. Individuals at risk of developing anxiety and depression should be identified, and targeted support should be provided. Future large-scale studies with long-term follow-up are required to validate and extend these findings.
Topics: Child; Humans; Infant; Child, Preschool; Depression; Quality of Life; Spinal Cord Injuries; Paraplegia; Anxiety
PubMed: 38143027
DOI: 10.1016/j.wneu.2023.12.092 -
The Cochrane Database of Systematic... Oct 2017Symptomatic vitreomacular adhesion (sVMA) is a recognised cause of visual loss and by tradition has been managed by pars plana vitrectomy (PPV). A less invasive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Symptomatic vitreomacular adhesion (sVMA) is a recognised cause of visual loss and by tradition has been managed by pars plana vitrectomy (PPV). A less invasive alternative to surgery in some people is enzymatic vitreolysis, using an intravitreal injection of ocriplasmin.
OBJECTIVES
To assess the efficacy and safety of ocriplasmin compared to no treatment, sham or placebo for the treatment of sVMA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 1), MEDLINE Ovid (1946 to 24 February 2017), Embase Ovid (1947 to 24 February 2017), PubMed (1946 to 24 February 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 24 February 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 24 February 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 24 February 2017. We did not use any date or language restrictions in the electronic searches for trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people with sVMA. The intervention was intravitreal ocriplasmin 125 μg injection, and this was compared to placebo or sham injection (control). Placebo was defined as a single intravitreal injection of 0.10 mL placebo with identical drug vehicle diluted with saline. A sham injection was defined as the syringe hub or blunt needle touching the conjunctiva to simulate an injection.
DATA COLLECTION AND ANALYSIS
Two authors independently selected relevant trials, assessed methodological quality and extracted data. We graded the certainty of the evidence using the GRADE approach.
MAIN RESULTS
This review included four RCTs conducted in Europe and the USA with a total of 932 eyes of 932 participants. Participants were 18 to 97 years of age, with evidence of focal vitreomacular adhesion (VMA) on optical coherence tomography (OCT) imaging, with a best corrected visual acuity (BCVA) of 20/25 or worse in the study eye and 20/400 or better in the fellow eye. The interventions compared were intravitreal ocriplasmin versus sham (two RCTs) or placebo (two RCTs) injection. Both sham and placebo injection were classified as the control group. The main outcome measures were assessed at 28 days and six months. Overall, we judged the studies to have a low or unclear risk of bias. All four RCTs were sponsored by the manufacturers of ocriplasmin.Compared with control, ocriplasmin treatment was more likely to result in VMA release within 28 days (risk ratio (RR) 3.46, 95% confidence interval (CI) 2.00 to 6.00; 859 eyes, 4 RCTs, high-certainty evidence). Approximately 97/1000 eyes will have VMA release within 28 days without treatment. An additional 237 eyes will have VMA release within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 96 more to 482 more).Treatment with ocriplasmin was also more likely to result in macular hole closure (RR 2.87, 95% CI 1.50 to 5.51; 229 eyes, 3 RCTs, high-certainty evidence). Approximately 123/1000 eyes with macular holes will have closure with no treatment. An additional 231 eyes will have macular hole closure for every 1000 eyes treated with ocriplasmin (95% CI 62 more to 556 more).Eyes receiving ocriplasmin were also more likely to have complete posterior vitreous detachment (PVD) within 28 days (RR 2.94, 95% CI 1.39 to 6.24; 689 eyes, 3 RCTs, high-certainty evidence). Approximately 40/1000 eyes will have complete PVD within 28 days without treatment. An additional 78 eyes will have complete PVD within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 16 more to 210 more).Eyes receiving ocriplasmin were more likely to achieve 3-line or greater improvement in BCVA at six months (RR 1.95, 95% CI 1.07 to 3.53; 674 eyes, 3 RCTs, moderate-certainty evidence). Approximately 61/1000 eyes will have a 3-line or greater improvement in BCVA at six months without treatment. An additional 58 eyes will have 3-line or greater improvement in BCVA at six months for every 1000 eyes treated with ocriplasmin (95% CI 9 more to 154 more).Receiving ocriplasmin also reduced the requirement for vitrectomy at six months (RR 0.67, 95% CI 0.50 to 0.91; 689 eyes, 3 RCTs, moderate-certainty evidence). Approximately 265/1000 eyes will require vitrectomy at six months without treatment and 87 fewer eyes will require vitrectomy for every 1000 eyes treated with ocriplasmin (95% CI 24 fewer to 132 fewer).Treatment with ocriplasmin resulted in a greater improvement in validated Visual Function Questionnaire form score at six months (mean improvement difference 2.7 points, 95% CI 0.8 to 4.6; 652 eyes, 2 RCTs, moderate-certainty evidence).Eyes receiving ocriplasmin were more likely to have an adverse event (RR 1.22, 95% CI 1.09 to 1.37, 909 eyes, 4 RCTs, moderate-certainty evidence). Approximately 571/1000 eyes will have an adverse event with sham or placebo injection and 106 more eyes will have an adverse event for every 1000 eyes treated with ocriplasmin (95% CI 52 more to 212 more).
AUTHORS' CONCLUSIONS
Evidence from a limited number of RCTs suggests that ocriplasmin is useful in the treatment of sVMA. However, up to 20% of eyes treated with ocriplasmin will still require additional treatment with PPV within six months. There were more ocular adverse events in eyes treated with ocriplasmin than control (sham or placebo injection) treatment. Many of these adverse events, particularly vitreous floaters and photopsia, are known to be associated with posterior vitreous detachment. At present however, there is minimal published long-term safety data on eyes treated with ocriplasmin. Further large RCTs comparing ocriplasmin with other management options for sVMA would be beneficial.
Topics: Adult; Aged; Aged, 80 and over; Fibrinolysin; Fibrinolytic Agents; Humans; Intravitreal Injections; Middle Aged; Peptide Fragments; Randomized Controlled Trials as Topic; Retinal Diseases; Time Factors; Tissue Adhesions; Visual Acuity; Vitrectomy; Vitreous Body; Vitreous Detachment
PubMed: 29040800
DOI: 10.1002/14651858.CD011874.pub2 -
The Cochrane Database of Systematic... Sep 2016Acne vulgaris is a very common skin problem that presents with blackheads, whiteheads, and inflamed spots. It frequently results in physical scarring and may cause... (Review)
Review
BACKGROUND
Acne vulgaris is a very common skin problem that presents with blackheads, whiteheads, and inflamed spots. It frequently results in physical scarring and may cause psychological distress. The use of oral and topical treatments can be limited in some people due to ineffectiveness, inconvenience, poor tolerability or side-effects. Some studies have suggested promising results for light therapies.
OBJECTIVES
To explore the effects of light treatment of different wavelengths for acne.
SEARCH METHODS
We searched the following databases up to September 2015: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We searched ISI Web of Science and Dissertation Abstracts International (from inception). We also searched five trials registers, and grey literature sources. We checked the reference lists of studies and reviews and consulted study authors and other experts in the field to identify further references to relevant randomised controlled trials (RCTs). We updated these searches in July 2016 but these results have not yet been incorporated into the review.
SELECTION CRITERIA
We included RCTs of light for treatment of acne vulgaris, regardless of language or publication status.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 71 studies, randomising a total of 4211 participants.Most studies were small (median 31 participants) and included participants with mild to moderate acne of both sexes and with a mean age of 20 to 30 years. Light interventions differed greatly in wavelength, dose, active substances used in photodynamic therapy (PDT), and comparator interventions (most commonly no treatment, placebo, another light intervention, or various topical treatments). Numbers of light sessions varied from one to 112 (most commonly two to four). Frequency of application varied from twice daily to once monthly.Selection and performance bias were unclear in the majority of studies. Detection bias was unclear for participant-assessed outcomes and low for investigator-assessed outcomes in the majority of studies. Attrition and reporting bias were low in over half of the studies and unclear or high in the rest. Two thirds of studies were industry-sponsored; study authors either reported conflict of interest, or such information was not declared, so we judged the risk of bias as unclear.Comparisons of most interventions for our first primary outcome 'Participant's global assessment of improvement' were not possible due to the variation in the interventions and the way the studies' outcomes were measured. We did not combine the effect estimates but rated the quality of the evidence as very low for the comparison of light therapies, including PDT to placebo, no treatment, topical treatment or other comparators for this outcome. One study which included 266 participants with moderate to severe acne showed little or no difference in effectiveness for this outcome between 20% aminolevulinic acid (ALA)-PDT (activated by blue light) versus vehicle plus blue light (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.72 to 1.04, low-quality evidence). A study (n = 180) of a comparison of ALA-PDT (activated by red light) concentrations showed 20% ALA was no more effective than 15% (RR 1.05, 95% CI 0.96 to 1.15) but better than 10% ALA (RR 1.22, 95% CI 1.05 to 1.42) and 5% ALA (RR 1.47, 95% CI 1.19 to 1.81). The number needed to treat for an additional beneficial outcome (NNTB) was 6 (95% CI 3 to 19) and 4 (95% CI 2 to 6) for the comparison of 20% ALA with 10% and 5% ALA, respectively.For our second primary outcome 'Investigator-assessed changes in lesion counts', we combined three RCTs, with 360 participants with moderate to severe acne and found methyl aminolevulinate (MAL) PDT (activated by red light) was no different to placebo cream plus red light with regard to change in inflamed lesions (ILs) (mean difference (MD) -2.85, 95% CI -7.51 to 1.81), percentage change in ILs (MD -10.09, 95% CI -20.25 to 0.06), change in non-inflamed lesions (NILs) (MD -2.01, 95% CI -7.07 to 3.05), or in percentage change in NILs (MD -8.09, 95% CI -21.51 to 5.32). We assessed the evidence as moderate quality for these outcomes meaning that there is little or no clinical difference between these two interventions for lesion counts.Studies comparing the effects of other interventions were inconsistent or had small samples and high risk of bias. We performed only narrative synthesis for the results of the remaining trials, due to great variation in many aspects of the studies, poor reporting, and failure to obtain necessary data. Several studies compared yellow light to placebo or no treatment, infrared light to no treatment, gold microparticle suspension to vehicle, and clindamycin/benzoyl peroxide combined with pulsed dye laser to clindamycin/benzoyl peroxide alone. There were also several other studies comparing MAL-PDT to light-only treatment, to adapalene and in combination with long-pulsed dye laser to long-pulsed dye laser alone. None of these showed any clinically significant effects.Our third primary outcome was 'Investigator-assessed severe adverse effects'. Most studies reported adverse effects, but not adequately with scarring reported as absent, and blistering reported only in studies on intense pulsed light, infrared light and photodynamic therapies. We rated the quality of the evidence as very low, meaning we were uncertain of the adverse effects of the light therapies.Although our primary endpoint was long-term outcomes, less than half of the studies performed assessments later than eight weeks after final treatment. Only a few studies assessed outcomes at more than three months after final treatment, and longer-term assessments are mostly not covered in this review.
AUTHORS' CONCLUSIONS
High-quality evidence on the use of light therapies for people with acne is lacking. There is low certainty of the usefulness of MAL-PDT (red light) or ALA-PDT (blue light) as standard therapies for people with moderate to severe acne.Carefully planned studies, using standardised outcome measures, comparing the effectiveness of common acne treatments with light therapies would be welcomed, together with adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.
PubMed: 27670126
DOI: 10.1002/14651858.CD007917.pub2 -
Nanoscale Advances Jan 2023: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and... (Review)
Review
: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and release drugs selectively at desired sites using targeting or sensing strategies. As drug carriers, they could improve therapeutic outcomes while reducing systemic toxicity. They have also shown promise in improving leukemia detection and diagnosis. The study aimed to assess the potential of nanotechnology-based diagnostics and therapeutics in preclinical human acute lymphoblastic leukemia (h-ALL). : We performed a systematic search through April 2022. Articles written in English reporting the toxicity, efficacy, and safety of nanotechnology-based drugs (in the aspect of treatment) and specificity, limit of detection (LOD), or sensitivity (in the aspect of the detection field) in preclinical h-ALL were included. The study was performed according to PRISMA instructions. The methodological quality was assessed using the QualSyst tool. : A total of 63 original articles evaluating nanotechnology-based therapeutics and 35 original studies evaluating nanotechnology-based diagnostics were included in this review. As therapeutics in ALL, nanomaterials offer controlled release, targeting or sensing ligands, targeted gene therapy, photodynamic therapy and photothermic therapy, and reversal of multidrug-resistant ALL. A narrative synthesis of studies revealed that nanoparticles improve the ratio of efficacy to the toxicity of anti-leukemic drugs. They have also been developed as a vehicle for biomolecules (such as antibodies) that can help detect and monitor leukemic biomarkers. Therefore, nanomaterials can help with early diagnostics and personalized treatment of ALL. : This review discussed nanotechnology-based preclinical strategies to achieve ALL diagnosis and therapy advancement. This involves modern drug delivery apparatuses and detection devices for prompt and targeted disease diagnostics. Nonetheless, we are yet in the experimental phase and investigational stage in the field of nanomedicine, with many features remained to be discovered as well as numerous problems to be solved.
PubMed: 36756502
DOI: 10.1039/d2na00483f -
Drug and Alcohol Review Nov 2022Policy enforcement is crucial to achieve impacts on alcohol-related harm. It is not clear what level of enforcement intensity or 'dosage' is necessary for addressing... (Review)
Review
ISSUES
Policy enforcement is crucial to achieve impacts on alcohol-related harm. It is not clear what level of enforcement intensity or 'dosage' is necessary for addressing drink driving and related harms. Given competing enforcement demands and agencies' resource constraints, understanding how much enforcement is sufficient to deter drink driving is critical.
APPROACH
This systematic literature review followed Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) guidelines to examine research about dosage effects of enforcement and related visibility on drink-driving outcomes, including motor vehicle crashes and fatalities. Risk of bias was assessed using the Cochrane Collaboration Effective Practice and Organization of Care tool and the JBI checklist.
KEY FINDINGS
The 21 studies that met the inclusion criteria for this review differed in measures of enforcement dosage and outcomes, making it difficult to synthesise results across studies and draw conclusions about a threshold or optimal level of enforcement. Although most included studies found that sustained enforcement was associated with reductions in drink driving or related harms, only two studies tested an optimal dosage. Due to study design limitations, a substantial percentage of these studies must be considered with caution.
IMPLICATIONS
Additional research with rigorous study designs with appropriate controls is needed to determine an optimal high visibility enforcement dosage level to help law enforcement agencies make realistic decisions about allocating enforcement resources to address drink driving.
CONCLUSION
Consistent evidence about a drink-driving enforcement dosage threshold is lacking, partly due to an insufficient number of well-designed studies. Addressing challenges of conducting rigorous studies in community settings is crucial.
Topics: Humans; Accidents, Traffic; Alcohol Drinking; Automobile Driving; Driving Under the Influence; Law Enforcement
PubMed: 35894270
DOI: 10.1111/dar.13519 -
The Cochrane Database of Systematic... May 2017Molluscum contagiosum is a common skin infection that is caused by a pox virus and occurs mainly in children. The infection usually resolves within months in people... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Molluscum contagiosum is a common skin infection that is caused by a pox virus and occurs mainly in children. The infection usually resolves within months in people without immune deficiency, but treatment may be preferred for social and cosmetic reasons or to avoid spreading the infection. A clear evidence base supporting the various treatments is lacking.This is an update of a Cochrane Review first published in 2006, and updated previously in 2009.
OBJECTIVES
To assess the effects of specific treatments and management strategies, including waiting for natural resolution, for cutaneous, non-genital molluscum contagiosum in people without immune deficiency.
SEARCH METHODS
We updated our searches of the following databases to July 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched six trial registers and checked the reference lists of included studies and review articles for further references to relevant randomised controlled trials. We contacted pharmaceutical companies and experts in the field to identify further relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of any treatment of molluscum contagiosum in people without immune deficiency. We excluded trials on sexually transmitted molluscum contagiosum and in people with immune deficiency (including those with HIV infection).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We obtained missing data from study authors where possible.
MAIN RESULTS
We found 11 new studies for this update, resulting in 22 included studies with a total of 1650 participants. The studies examined the effects of topical (20 studies) and systemic interventions (2 studies).Among the new included studies were the full trial reports of three large unpublished studies, brought to our attention by an expert in the field. They all provided moderate-quality evidence for a lack of effect of 5% imiquimod compared to vehicle (placebo) on short-term clinical cure (4 studies, 850 participants, 12 weeks after start of treatment, risk ratio (RR) 1.33, 95% confidence interval (CI) 0.92 to 1.93), medium-term clinical cure (2 studies, 702 participants, 18 weeks after start of treatment, RR 0.88, 95% CI 0.67 to 1.14), and long-term clinical cure (2 studies, 702 participants, 28 weeks after start of treatment, RR 0.97, 95% CI 0.79 to 1.17). We found similar but more certain results for short-term improvement (4 studies, 850 participants, 12 weeks after start of treatment, RR 1.14, 95% CI 0.89 to 1.47; high-quality evidence). For the outcome 'any adverse effect', we found high-quality evidence for little or no difference between topical 5% imiquimod and vehicle (3 studies, 827 participants, RR 0.97, 95% CI 0.88 to 1.07), but application site reactions were more frequent in the groups treated with imiquimod (moderate-quality evidence): any application site reaction (3 studies, 827 participants, RR 1.41, 95% CI 1.13 to 1.77, the number needed to treat for an additional harmful outcome (NNTH) was 11); severe application site reaction (3 studies, 827 participants, RR 4.33, 95% CI 1.16 to 16.19, NNTH over 40).For the following 11 comparisons, there was limited evidence to show which treatment was superior in achieving short-term clinical cure (low-quality evidence): 5% imiquimod less effective than cryospray (1 study, 74 participants, RR 0.60, 95% CI 0.46 to 0.78) and 10% potassium hydroxide (2 studies, 67 participants, RR 0.65, 95% CI 0.46 to 0.93); 10% Australian lemon myrtle oil more effective than olive oil (1 study, 31 participants, RR 17.88, 95% CI 1.13 to 282.72); 10% benzoyl peroxide cream more effective than 0.05% tretinoin (1 study, 30 participants, RR 2.20, 95% CI 1.01 to 4.79); 5% sodium nitrite co-applied with 5% salicylic acid more effective than 5% salicylic acid alone (1 study, 30 participants, RR 3.50, 95% CI 1.23 to 9.92); and iodine plus tea tree oil more effective than tea tree oil (1 study, 37 participants, RR 0.20, 95% CI 0.07 to 0.57) or iodine alone (1 study, 37 participants, RR 0.07, 95% CI 0.01 to 0.50). Although there is some uncertainty, 10% potassium hydroxide appears to be more effective than saline (1 study, 20 participants, RR 3.50, 95% CI 0.95 to 12.90); homeopathic calcarea carbonica appears to be more effective than placebo (1 study, 20 participants, RR 5.57, 95% CI 0.93 to 33.54); 2.5% appears to be less effective than 5% solution of potassium hydroxide (1 study, 25 participants, RR 0.35, 95% CI 0.12 to 1.01); and 10% povidone iodine solution plus 50% salicylic acid plaster appears to be more effective than salicylic acid plaster alone (1 study, 30 participants, RR 1.43, 95% CI 0.95 to 2.16).We found no statistically significant differences for other comparisons (most of which addressed two different topical treatments). We found no randomised controlled trial evidence for expressing lesions or topical hydrogen peroxide.Study limitations included no blinding, many dropouts, and no intention-to-treat analysis. Except for the severe application site reactions of imiquimod, none of the evaluated treatments described above were associated with serious adverse effects (low-quality evidence). Among the most common adverse events were pain during application, erythema, and itching. Included studies of the following comparisons did not report adverse effects: calcarea carbonica versus placebo, 10% povidone iodine plus 50% salicylic acid plaster versus salicylic acid plaster, and 10% benzoyl peroxide versus 0.05% tretinoin.We were unable to judge the risk of bias in most studies due to insufficient information, especially regarding concealment of allocation and possible selective reporting. We considered five studies to be at low risk of bias.
AUTHORS' CONCLUSIONS
No single intervention has been shown to be convincingly effective in the treatment of molluscum contagiosum. We found moderate-quality evidence that topical 5% imiquimod was no more effective than vehicle in terms of clinical cure, but led to more application site reactions, and high-quality evidence that there was no difference between the treatments in terms of short-term improvement. However, high-quality evidence showed a similar number of general side effects in both groups. As the evidence found did not favour any one treatment, the natural resolution of molluscum contagiosum remains a strong method for dealing with the condition.
Topics: Adjuvants, Immunologic; Aminoquinolines; Anti-Infective Agents, Local; Benzoyl Peroxide; Cimetidine; Humans; Hydroxides; Imiquimod; Molluscum Contagiosum; Myrtus; Olive Oil; Phytotherapy; Plant Oils; Potassium Compounds; Povidone-Iodine; Randomized Controlled Trials as Topic; Remission, Spontaneous; Salicylic Acid; Sodium Nitrite
PubMed: 28513067
DOI: 10.1002/14651858.CD004767.pub4