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JAMA Nov 2023Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality.
OBJECTIVE
To compare efficacy and comparative efficacy of therapies for alcohol use disorder.
DATA SOURCES
PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023.
STUDY SELECTION
For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit.
MAIN OUTCOMES AND MEASURES
The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms.
RESULTS
Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo.
CONCLUSIONS AND RELEVANCE
In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.
Topics: Humans; Acamprosate; Alcohol Drinking; Alcoholism; Drug-Related Side Effects and Adverse Reactions; Naltrexone; Prospective Studies; Quality of Life; United States; Alcohol Deterrents; Psychosocial Intervention
PubMed: 37934220
DOI: 10.1001/jama.2023.19761 -
Journal of Psychiatric Research Apr 2020To conduct a systematic review and meta-analysis of literature from large databases and registries to assess the effects of ADHD medication on associated functional... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a systematic review and meta-analysis of literature from large databases and registries to assess the effects of ADHD medication on associated functional outcomes.
STUDY DESIGN
A literature search was performed in PubMed, PsycINFO, MEDLINE, and Web of Science for articles published prior to January 2019. Sample size, age range, country of origin, medication type, number of functional events and non-events, odds ratios and hazard ratios, and means and standard deviations were extracted. Random-effects meta-analyses were conducted for 21 studies examining functional outcomes.
RESULTS
40 articles were included. The majority suggest a robust protective effect of ADHD medication treatment on mood disorders, suicidality, criminality, substance use disorders, accidents and injuries, traumatic brain injuries, motor vehicle crashes, and educational outcomes. Similarly, the meta-analyses demonstrated a protective effect of medication treatment on academic outcomes, accidents and injuries, and mood disorders.
CONCLUSIONS
These findings suggest that ADHD medication treatments are associated with decreases in the risks for a wide range of ADHD-associated functional outcomes supporting efforts aimed at early diagnosis and treatment of individuals with ADHD.
Topics: Accidents, Traffic; Attention Deficit Disorder with Hyperactivity; Databases, Factual; Humans; Odds Ratio; Proportional Hazards Models
PubMed: 32014701
DOI: 10.1016/j.jpsychires.2020.01.006 -
The Cochrane Database of Systematic... Oct 2022Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such... (Review)
Review
BACKGROUND
Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks).
OBJECTIVES
To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA).
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED. Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting. Findings Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI -10.47 to 13.67; very low certainty evidence). Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD -0.33, 95% CI -0.51 to -0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI -0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI -0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI -0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores. Adverse effects The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects. AUTHORS' CONCLUSIONS: Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Adrenal Cortex Hormones; Cataract; Cyclosporine; Dry Eye Syndromes; Glucocorticoids; Loteprednol Etabonate; Lubricant Eye Drops; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 36269562
DOI: 10.1002/14651858.CD015070.pub2 -
JPEN. Journal of Parenteral and Enteral... 2014Parenteral nutrition (PN) is a high-alert medication available for patient care within a complex clinical process. Beyond application of best practice recommendations to... (Review)
Review
BACKGROUND
Parenteral nutrition (PN) is a high-alert medication available for patient care within a complex clinical process. Beyond application of best practice recommendations to guide safe use and optimize clinical outcome, several issues are better addressed through evidence-based policies, procedures, and practices. This document provides evidence-based guidance for clinical practices involving PN prescribing, order review, and preparation.
METHOD
A systematic review of the best available evidence was used by an expert work group to answer a series of questions about PN prescribing, order review, compounding, labeling, and dispensing. Concepts from the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) format were applied as appropriate. The specific clinical guideline recommendations were developed using consensus prior to review and approval by the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. The following questions were addressed: (1) Does education of prescribers improve PN ordering? (2) What is the maximum safe osmolarity of PN admixtures intended for peripheral vein administration? (3) What are the appropriate calcium intake and calcium-phosphate ratios in PN for optimal neonatal bone mineralization? (4) What are the clinical advantages or disadvantages of commercially available premade ("premixed") multichambered PN formulations compared with traditional/customized PN formulations? (5) What are the clinical (infection, catheter occlusion) advantages or disadvantages of 2-in-1 compared with 3-in-1 PN admixtures? (6) What macronutrient dosing limits are expected to provide for the most stable 3-in-1 admixtures? (7) What are the most appropriate recommendations for optimizing calcium (gluconate) and (Na- or K-) phosphate compatibility in PN admixtures? (8) What micronutrient contamination is present in parenteral stock solutions currently used to compound PN admixtures? (9) Is it safe to use the PN admixture as a vehicle for non-nutrient medication delivery? (10) Should heparin be included in the PN admixture to reduce the risk of central vein thrombosis? (11) What methods of repackaging intravenous fat emulsion (IVFE) into smaller patient-specific volumes are safe? (12) What beyond-use date should be used for (a) IVFE dispensed for separate infusion in the original container and (b) repackaged IVFE?
Topics: Drug Compounding; Drug Prescriptions; Humans; Infusions, Parenteral; Parenteral Nutrition; Parenteral Nutrition Solutions; Randomized Controlled Trials as Topic; Societies, Medical
PubMed: 24531708
DOI: 10.1177/0148607114521833 -
The Cochrane Database of Systematic... Feb 2017Eczema is a chronic skin disease characterised by dry skin, intense itching, inflammatory skin lesions, and a considerable impact on quality of life. Moisturisation is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eczema is a chronic skin disease characterised by dry skin, intense itching, inflammatory skin lesions, and a considerable impact on quality of life. Moisturisation is an integral part of treatment, but it is unclear if moisturisers are effective.
OBJECTIVES
To assess the effects of moisturisers for eczema.
SEARCH METHODS
We searched the following databases to December 2015: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, the GREAT database. We searched five trials registers and checked references of included and excluded studies for further relevant trials.
SELECTION CRITERIA
Randomised controlled trials in people with eczema.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We included 77 studies (6603 participants, mean age: 18.6 years, mean duration: 6.7 weeks). We assessed 36 studies as at a high risk of bias, 34 at unclear risk, and seven at low risk. Twenty-four studies assessed our primary outcome 'participant-assessed disease severity', 13 assessed 'satisfaction', and 41 assessed 'adverse events'. Secondary outcomes included investigator-assessed disease severity (addressed in 65 studies), skin barrier function (29), flare prevention (16), quality of life (10), and corticosteroid use (eight). Adverse events reporting was limited (smarting, stinging, pruritus, erythema, folliculitis).Six studies evaluated moisturiser versus no moisturiser. 'Participant-assessed disease severity' and 'satisfaction' were not assessed. Moisturiser use yielded lower SCORAD than no moisturiser (three studies, 276 participants, mean difference (MD) -2.42, 95% confidence interval (CI) -4.55 to -0.28), but the minimal important difference (MID) (8.7) was unmet. There were fewer flares with moisturisers (two studies, 87 participants, RR 0.40, 95% CI 0.23 to 0.70), time to flare was prolonged (median: 180 versus 30 days), and less topical corticosteroids were needed (two studies, 222 participants, MD -9.30 g, 95% CI -15.3 to -3.27). There was no statistically significant difference in adverse events (one study, 173 participants, risk ratio (RR) 15.34, 95% CI 0.90 to 261.64). Evidence for these outcomes was low quality.With Atopiclair (three studies), 174/232 participants experienced improvement in participant-assessed disease severity versus 27/158 allocated to vehicle (RR 4.51, 95% CI 2.19 to 9.29). Atopiclair decreased itching (four studies, 396 participants, MD -2.65, 95% CI -4.21 to -1.09) and achieved more frequent satisfaction (two studies, 248 participants, RR 2.14, 95% CI 1.58 to 2.89), fewer flares (three studies, 397 participants, RR 0.18, 95% CI 0.11 to 0.31), and lower EASI (four studies, 426 participants, MD -4.0, 95% CI -5.42 to -2.57), but MID (6.6) was unmet. The number of participants reporting adverse events was not statistically different (four studies, 430 participants, RR 1.03, 95% CI 0.79 to 1.33). Evidence for these outcomes was moderate quality.Participants reported skin improvement more frequently with urea-containing cream than placebo (one study, 129 participants, RR 1.28, 95% CI 1.06 to 1.53; low-quality evidence), with equal satisfaction between the two groups (one study, 38 participants, low-quality evidence). Urea-containing cream improved dryness (investigator-assessed) more frequently (one study, 128 participants, RR 1.40, 95% CI 1.14 to 1.71; moderate-quality evidence) with fewer flares (one study, 44 participants, RR 0.47, 95% CI 0.24 to 0.92; low-quality evidence), but more participants in this group reported adverse events (one study, 129 participants, RR 1.65, 95% CI 1.16 to 2.34; moderate-quality evidence).Three studies assessed glycerol-containing moisturiser versus vehicle or placebo. More participants in the glycerol group noticed skin improvement (one study, 134 participants, RR 1.22, 95% CI 1.01 to 1.48; moderate-quality evidence), and this group saw improved investigator-assessed SCORAD (one study, 249 participants, MD -2.20, 95% CI -3.44 to -0.96; high-quality evidence), but MID was unmet. Participant satisfaction was not addressed. The number of participants reporting adverse events was not statistically significant (two studies, 385 participants, RR 0.90, 95% CI 0.68 to 1.19; moderate-quality evidence).Four studies investigated oat-containing moisturisers versus no treatment or vehicle. No significant differences between groups were reported for participant-assessed disease severity (one study, 50 participants, RR 1.11, 95% CI 0.84 to 1.46; low-quality evidence), satisfaction (one study, 50 participants, RR 1.06, 95% CI 0.74 to 1.52; very low-quality evidence), and investigator-assessed disease severity (three studies, 272 participants, standardised mean difference (SMD) -0.23, 95% CI -0.66 to 0.21; low-quality evidence). In the oat group, there were fewer flares (one study, 43 participants, RR 0.31, 95% CI 0.12 to 0.7; low-quality evidence) and less topical corticosteroids needed (two studies, 222 participants, MD -9.30g, 95% CI 15.3 to -3.27; low-quality evidence), but more adverse events were reported (one study, 173 participants; Peto odds ratio (OR) 7.26, 95% CI 1.76 to 29.92; low-quality evidence).All moisturisers above were compared to placebo, vehicle, or no moisturiser. Participants considered moisturisers more effective in reducing eczema (five studies, 572 participants, RR 2.46, 95% CI 1.16 to 5.23; low-quality evidence) and itch (seven studies, 749 participants, SMD -1.10, 95% CI -1.83 to -0.38) than control. Participants in both treatment arms reported comparable satisfaction (three studies, 296 participants, RR 1.35, 95% CI 0.77 to 2.26; low-quality evidence). Moisturisers led to lower investigator-assessed disease severity (12 studies, 1281 participants, SMD -1.04, 95% CI -1.57 to -0.51; high-quality evidence) and fewer flares (six studies, 607 participants, RR 0.33, 95% CI 0.17 to 0.62; moderate-quality evidence), but there was no difference in adverse events (10 studies, 1275 participants, RR 1.03, 95% CI 0.82 to 1.30; moderate-quality evidence).Topical active treatment combined with moisturiser was more effective than active treatment alone in reducing investigator-assessed disease severity (three studies, 192 participants, SMD -0.87, 95% CI -1.17 to -0.57; moderate-quality evidence) and flares (one study, 105 participants, RR 0.43, 95% CI 0.20 to 0.93), and was preferred by participants (both low-quality evidence). There was no statistically significant difference in number of adverse events (one study, 125 participants, RR 0.39, 95% CI 0.13 to 1.19; very low-quality evidence). Participant-assessed disease severity was not addressed.
AUTHORS' CONCLUSIONS
Most moisturisers showed some beneficial effects, producing better results when used with active treatment, prolonging time to flare, and reducing the number of flares and amount of topical corticosteroids needed to achieve similar reductions in eczema severity. We did not find reliable evidence that one moisturiser is better than another.
Topics: Adrenal Cortex Hormones; Eczema; Emollients; Humans; Patient Satisfaction; Randomized Controlled Trials as Topic; Severity of Illness Index; Symptom Flare Up
PubMed: 28166390
DOI: 10.1002/14651858.CD012119.pub2 -
The Cochrane Database of Systematic... Apr 2015Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules and dilated blood vessels. The eyes are often... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules and dilated blood vessels. The eyes are often involved and thickening of the skin with enlargement (phymas), especially of the nose, can occur in some people. A range of treatment options are available but it is unclear which are most effective.
OBJECTIVES
To assess the efficacy and safety of treatments for rosacea.
SEARCH METHODS
We updated our searches, to July 2014, of: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974) and Science Citation Index (from 1988). We searched five trials registers and checked reference lists for further relevant studies.
SELECTION CRITERIA
Randomised controlled trials in people with moderate to severe rosacea.
DATA COLLECTION AND ANALYSIS
Study selection, data extraction, risk of bias assessment and analyses were carried out independently by two authors.
MAIN RESULTS
We included 106 studies, comprising 13,631 participants. Sample sizes of 30-100 and study duration of two to three months were most common. More women than men were included, mean age of 48.6 years, and the majority had papulopustular rosacea, followed by erythematotelangiectatic rosacea.A wide range of comparisons (67) were evaluated. Topical interventions: metronidazole, azelaic acid, ivermectin, brimonidine or other topical treatments. Systemic interventions: oral antibiotics, combinations with topical treatments or other systemic treatments, i.e. isotretinoin. Several studies evaluated laser or light-based treatment.The majority of studies (57/106) were assessed as 'unclear risk of bias', 37 'high risk ' and 12 'low risk'. Twenty-two studies provided no usable or retrievable data i.e. none of our outcomes were addressed, no separate data reported for rosacea or limited data in abstracts.Eleven studies assessed our primary outcome 'change in quality of life', 52 studies participant-assessed changes in rosacea severity and almost all studies addressed adverse events, although often only limited data were provided. In most comparisons there were no statistically significant differences in number of adverse events, most were mild and transient. Physician assessments including investigators' global assessments, lesion counts and erythema were evaluated in three-quarters of the studies, but time needed for improvement and duration of remission were incompletely or not reported.The quality of the body of evidence was rated moderate to high for most outcomes, but for some outcomes low to very low.Data for several outcomes could only be pooled for topical metronidazole and azelaic acid. Both were shown to be more effective than placebo in papulopustular rosacea (moderate quality evidence for metronidazole and high for azelaic acid). Pooled data from physician assessments in three trials demonstrated that metronidazole was more effective compared to placebo (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.29 to 3.02). Four trials provided data on participants' assessments, illustrating that azelaic acid was more effective than placebo (RR 1.46, 95% CI 1.30 to 1.63). The results from three studies were contradictory on which of these two treatments was most effective.Two studies showed a statistically significant and clinically important improvement in favour of topical ivermectin when compared to placebo (high quality evidence). Participants' assessments in these studies showed a RR of 1.78 (95% CI 1.50 to 2.11) and RR of 1.92 (95% CI 1.59 to 2.32),which were supported by physicians' assessments. Topical ivermectin appeared to be slightly more effective than topical metronidazole for papulopustular rosacea, based on one study, for improving quality of life and participant and physician assessed outcomes (high quality evidence for these outcomes).Topical brimonidine in two studies was more effective than vehicle in reducing erythema in rosacea at all time points over 12 hours (high quality evidence). At three hours the participants' assessments had a RR of 2.21 (95% CI 1.52 to 3.22) and RR of 2.00 (95% CI 1.33 to 3.01) in favour of brimonidine. Physicians' assessments confirmed these data. There was no rebound or worsening of erythema after treatment cessation.Topical clindamycin phosphate combined with tretinoin was not considered to be effective compared to placebo (moderate quality evidence).Topical ciclosporin ophthalmic emulsion demonstrated effectiveness and improved quality of life for people with ocular rosacea (low quality evidence).Of the comparisons assessing oral treatments for papulopustular rosacea there was moderate quality evidence that tetracycline was effective but this was based on two old studies of short duration. Physician-based assessments in two trials indicated that doxycycline appeared to be significantly more effective than placebo (RR 1.59, 95% CI 1.02 to 2.47 and RR 2.37, 95% CI 1.12 to 4.99) (high quality evidence). There was no statistically significant difference in effectiveness between 100 mg and 40 mg doxycycline, but there was evidence of fewer adverse effects with the lower dose (RR 0.25, 95% CI 0.11 to 0.54) (low quality evidence). There was very low quality evidence from one study (assessed at high risk of bias) that doxycycline 100 mg was as effective as azithromycin. Low dose minocycline (45 mg) was effective for papulopustular rosacea (low quality evidence).Oral tetracycline was compared with topical metronidazole in four studies and showed no statistically significant difference between the two treatments for any outcome (low to moderate quality evidence).Low dose isotretinoin was considered by both the participants (RR 1.23, 95% CI 1.05 to 1.43) and physicians (RR 1.18, 95% CI 1.03 to 1.36) to be slightly more effective than doxycycline 50-100 mg (high quality evidence).Pulsed dye laser was more effective than yttrium-aluminium-garnet (Nd:YAG) laser based on one study, and it appeared to be as effective as intense pulsed light therapy (both low quality evidence).
AUTHORS' CONCLUSIONS
There was high quality evidence to support the effectiveness of topical azelaic acid, topical ivermectin, brimonidine, doxycycline and isotretinoin for rosacea. Moderate quality evidence was available for topical metronidazole and oral tetracycline. There was low quality evidence for low dose minocycline, laser and intense pulsed light therapy and ciclosporin ophthalmic emulsion for ocular rosacea. Time needed to response and response duration should be addressed more completely, with more rigorous reporting of adverse events. Further studies on treatment of ocular rosacea are warranted.
Topics: Anti-Infective Agents; Brimonidine Tartrate; Cyclosporine; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Female; Humans; Ivermectin; Male; Metronidazole; Middle Aged; Ophthalmic Solutions; Quinoxalines; Randomized Controlled Trials as Topic; Rosacea; Tetracycline
PubMed: 25919144
DOI: 10.1002/14651858.CD003262.pub5 -
JAMA May 2014Alcohol use disorders cause substantial morbidity and early mortality yet remain greatly undertreated. Medications are considerably underused. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Alcohol use disorders cause substantial morbidity and early mortality yet remain greatly undertreated. Medications are considerably underused.
OBJECTIVE
To conduct a systematic review and meta-analysis of the benefits and harms of medications (US FDA-approved and others) for adults with alcohol use disorders.
DATA SOURCES
PubMed, Cochrane Library, PsycINFO, CINAHL, EMBASE, FDA website, and clinical trials registries (January 1, 1970, to March 1, 2014).
STUDY SELECTION
Two reviewers selected randomized clinical trials (RCTs) with at least 12 weeks' duration that reported eligible outcomes and head-to-head prospective cohort studies reporting health outcomes or harms.
DATA EXTRACTION AND SYNTHESIS
We conducted meta-analyses using random-effects models and calculated numbers needed to treat for benefit (NNTs) or harm (NNHs).
MAIN OUTCOMES AND MEASURES
Alcohol consumption, motor vehicle crashes, injuries, quality of life, function, mortality, and harms.
RESULTS
We included 122 RCTs and 1 cohort study (total 22,803 participants). Most assessed acamprosate (27 studies, n = 7519), naltrexone (53 studies, n = 9140), or both. The NNT to prevent return to any drinking for acamprosate was 12 (95% CI, 8 to 26; risk difference [RD], -0.09; 95% CI, -0.14 to -0.04) and was 20 (95% CI, 11 to 500; RD, -0.05; 95% CI, -0.10 to -0.002) for oral naltrexone (50 mg/d). The NNT to prevent return to heavy drinking was 12 (95% CI, 8 to 26; RD -0.09; 95% CI, -0.13 to -0.04) for oral naltrexone (50 mg/d). Meta-analyses of trials comparing acamprosate to naltrexone found no statistically significant difference between them for return to any drinking (RD, 0.02; 95% CI, -0.03 to 0.08) or heavy drinking (RD, 0.01; 95% CI, -0.05 to 0.06). For injectable naltrexone, meta-analyses found no association with return to any drinking (RD, -0.04; 95% CI, -0.10 to 0.03) or heavy drinking (RD, -0.01; 95% CI, -0.14 to 0.13) but found an association with reduction in heavy drinking days (weighted mean difference [WMD], -4.6%; 95% CI, -8.5% to -0.56%). Among medications used off-label, moderate evidence supports an association with improvement in some consumption outcomes for nalmefene (heavy drinking days per month: WMD, -2.0; 95% CI, -3.0 to -1.0; drinks per drinking day: WMD, -1.02; 95% CI, -1.77 to -0.28) and topiramate (% heavy drinking days: WMD, -9.0%; 95% CI, -15.3% to -2.7%; drinks per drinking day: WMD, -1.0; 95% CI, -1.6 to -0.48). For naltrexone and nalmefene, NNHs for withdrawal from trials due to adverse events were 48 (95% CI, 30 to 112) and 12 (95% CI, 7 to 50), respectively; risk was not significantly increased for acamprosate or topiramate.
CONCLUSIONS AND RELEVANCE
Both acamprosate and oral naltrexone were associated with reduction in return to drinking. When directly compared with one another, no significant differences were found between acamprosate and naltrexone for controlling alcohol consumption. Factors such as dosing frequency, potential adverse events, and availability of treatments may guide medication choice.
Topics: Acamprosate; Alcohol-Related Disorders; Fructose; Harm Reduction; Humans; Naltrexone; Outpatients; Randomized Controlled Trials as Topic; Taurine; Topiramate
PubMed: 24825644
DOI: 10.1001/jama.2014.3628 -
The Cochrane Database of Systematic... Mar 2023Acute bacterial conjunctivitis is an infection of the conjunctiva and is one of the most common ocular disorders in primary care. Antibiotics are generally prescribed on... (Review)
Review
BACKGROUND
Acute bacterial conjunctivitis is an infection of the conjunctiva and is one of the most common ocular disorders in primary care. Antibiotics are generally prescribed on the basis that they may speed recovery, reduce persistence, and prevent keratitis. However, many cases of acute bacterial conjunctivitis are self-limited, resolving without antibiotic therapy. This Cochrane Review was first published in The Cochrane Library in 1999, then updated in 2006, 2012, and 2022.
OBJECTIVES
To assess the benefits and side effects of antibiotic therapy in the management of acute bacterial conjunctivitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2022, Issue 5), MEDLINE (January 1950 to May 2022), Embase (January 1980 to May 2022), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.
CLINICALTRIALS
gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases in May 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which any form of antibiotic treatment, with or without steroid, had been compared with placebo/vehicle in the management of acute bacterial conjunctivitis. This included topical and systemic antibiotic treatments.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed the titles and abstracts of identified studies. We assessed the full text of all potentially relevant studies and determined the included RCTs, which were further assessed for risk of bias using Cochrane methodology. We performed data extraction in a standardized manner and conducted random-effects meta-analyses using RevMan Web.
MAIN RESULTS
We included 21 eligible RCTs, 10 of which were newly identified in this update. A total of 8805 participants were randomized. All treatments were topical in the form of drops or ointment. The trials were heterogeneous in terms of their eligibility criteria, the nature of the intervention (antibiotic drug class, which included fluoroquinolones [FQs] and non-FQs; dosage frequency; duration of treatment), the outcomes assessed and the time points of assessment. We judged one trial to be of high risk of bias, four as low risk of bias, and the others as raising some concerns. Based on intention-to-treat (ITT) population, antibiotics likely improved clinical cure (resolution of clinical symptoms or signs) by 26% (RR 1.26, 95% CI 1.09 to 1.46; 5 trials, 1474 participants; moderate certainty) as compared with placebo. Subgroup analysis showed no differences by antibiotic class (P = 0.67) or treatment duration (P = 0.60). In the placebo group, 55.5% (408/735) of participants had spontaneous clinical resolution by days 4 to 9 versus 68.2% (504/739) of participants treated with an antibiotic. Based on modified ITT population, in which participants were analyzed after randomization on the basis of positive microbiological culture, antibiotics likely increased microbiological cure (RR 1.53, 95% CI 1.34 to 1.74; 10 trials, 2827 participants) compared with placebo at the end of therapy; there were no subgroup differences by drug class (P = 0.60). No study evaluated the cost-effectiveness of antibiotic treatment. Patients receiving antibiotics had a lower risk of treatment incompletion than those in the placebo group (RR 0.64, 95% CI 0.52 to 0.78; 13 trials, 5573 participants; moderate certainty) and were 27% less likely to have persistent clinical infection (RR 0.73, 95% CI 0.65 to 0.81; 19 trials, 5280 participants; moderate certainty). There was no evidence of serious systemic side effects reported in either the antibiotic or placebo group (very low certainty). When compared with placebo, FQs (RR 0.70, 95% CI 0.54 to 0.90) but not non-FQs (RR 4.05, 95% CI 1.36 to 12.00) may result in fewer participants with ocular side effects. However, the estimated effects were of very low certainty.
AUTHORS' CONCLUSIONS
The findings of this update suggest that the use of topical antibiotics is associated with a modestly improved chance of resolution in comparison to the use of placebo. Since no evidence of serious side effects was reported, use of antibiotics may therefore be considered to achieve better clinical and microbiologic efficacy than placebo. Increasing the proportion of participants with clinical cure or increasing the speed of recovery or both are important for individual return to work or school, allowing people to regain quality of life. Future studies may examine antiseptic treatments with topical antibiotics for reasons of cost and growing antibiotic resistance.
Topics: Humans; Anti-Bacterial Agents; Conjunctivitis, Bacterial; Randomized Controlled Trials as Topic
PubMed: 36912752
DOI: 10.1002/14651858.CD001211.pub4 -
Journal of Cosmetic Dermatology Oct 2023Topical azelaic acid (AA) is indicated for acne and rosacea, but there is some evidence for its use for other dermatological conditions. (Review)
Review
BACKGROUND
Topical azelaic acid (AA) is indicated for acne and rosacea, but there is some evidence for its use for other dermatological conditions.
AIMS
To assess the effectiveness and safety of topical AA for acne vulgaris, rosacea, hyperpigmentation/melasma, and skin aging.
METHODS
RCTs of at least 6 weeks' treatment duration were eligible for inclusion. Databases including MEDLINE, Embase, CINAHL, and ClinicalTrials.gov were searched up to December 2022. Two reviewers were involved in all stages of the systematic review process.
RESULTS
Forty-three RCTs met the inclusion criteria. Meta-analyses within 20 rosacea studies demonstrated that erythema severity, inflammatory lesion counts, overall improvement, and treatment success (achieving skin clarity) were significantly improved with AA compared with vehicle after 12 weeks. AA was more effective than metronidazole 0.75% for improved erythema severity, overall improvement, and inflammatory lesion counts. Sixteen acne studies suggest that AA is more effective than vehicle for improving global assessments and reducing acne severity. AA 20% also significantly reduced more lesions than erythromycin gel. Within seven melasma studies, AA 20% was significantly better than vehicle for both severity and global improvement. AA 20% demonstrated significantly better results compared with hydroquinone 2% for global improvement. Very few significant differences between AA and comparators were observed for commonly reported adverse events. No eligible RCTs were found that evaluated skin aging.
CONCLUSIONS
AA is more effective than vehicle for rosacea, acne and melasma. Comparisons between AA and other treatments were often equivalent. Where there is equivalence, AA may be a good option for some clinical situations. RCT evidence is needed to evaluate the effectiveness of AA on skin aging.
Topics: Humans; Skin Aging; Acne Vulgaris; Rosacea; Erythema; Treatment Outcome; Melanosis; Dermatologic Agents
PubMed: 37550898
DOI: 10.1111/jocd.15923 -
American Journal of Clinical Dermatology Jun 2019Topical retinoids are a first-line treatment for acne vulgaris.
BACKGROUND
Topical retinoids are a first-line treatment for acne vulgaris.
OBJECTIVE
This systematic review aims to evaluate the efficacy, safety, and tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris.
METHODS
A PubMed and Embase search was conducted using the search terms 'adapalene,' 'tretinoin,' 'tazarotene,' and 'acne vulgaris.' Selection of articles fit the following inclusion criteria: clinical trials evaluating both efficacy and safety/tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris and published between January 1, 2008 and September 1, 2018. Exclusion criteria included clinical trials involving 20 subjects or fewer, subjects under 12 years of age, and topical retinoid combination therapies with moisturizers or aloe vera. Of 424 search results found, a total of 54 clinical trials were chosen based on selection criteria.
RESULTS
Topical retinoids are superior to vehicle in improving Investigator Global Assessment and Investigator's Static Global Assessment (24.1-28.8% and 13.3-17.3%, respectively; p < 0.001). A topical retinoid combined with benzoyl peroxide led to IGA improvement compared with vehicle (26.1-34.9% vs 7-11.8%; p < 0.001) at Week 12. Topical retinoid plus an oral antibiotic was superior to vehicle in reducing lesion counts (64-78.9% vs 41-56.8%, p < 0.001). There was no significant difference in efficacy between tretinoin and tazarotene. Tretinoin 0.05% resulted in 62% of patients experiencing AEs compared with adapalene 0.1% (19%) and adapalene 0.3% (40%). More patients receiving adapalene were tolerant of the AEs compared with tazarotene (55.4% vs 24.4%; p < 0.0012).
CONCLUSIONS
Topical retinoids are safe and efficacious for the treatment of acne vulgaris. They should be used in combination with benzoyl peroxide to optimize results in patients. The differences in efficacy of topical retinoids appears minor; therefore, the type of topical retinoid is not as important as choosing a particular strength of topical retinoid and combining it with an antimicrobial agent. Adapalene has a superior tolerability profile amongst topical retinoids.
Topics: Acne Vulgaris; Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Benzoyl Peroxide; Clinical Trials as Topic; Dermatologic Agents; Drug Therapy, Combination; Humans; Retinoids; Severity of Illness Index; Treatment Outcome
PubMed: 30674002
DOI: 10.1007/s40257-019-00423-z