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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 -
The Cochrane Database of Systematic... Mar 2020Acne is a common, economically burdensome condition that can cause psychological harm and, potentially, scarring. Topical benzoyl peroxide (BPO) is a widely used acne... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acne is a common, economically burdensome condition that can cause psychological harm and, potentially, scarring. Topical benzoyl peroxide (BPO) is a widely used acne treatment; however, its efficacy and safety have not been clearly evaluated.
OBJECTIVES
To assess the effects of BPO for acne.
SEARCH METHODS
We searched the following databases up to February 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of relevant randomised controlled trials (RCTs) and systematic reviews.
SELECTION CRITERIA
We included RCTs that compared topical BPO used alone (including different formulations and concentrations of BPO) or as part of combination treatment against placebo, no treatment, or other active topical medications for clinically diagnosed acne (used alone or in combination with other topical drugs not containing BPO) on the face or trunk.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane. Primary outcome measures were 'participant global self-assessment of acne improvement' and 'withdrawal due to adverse events in the whole course of a trial'. 'Percentage of participants experiencing any adverse event in the whole course of a trial' was a key secondary outcome.
MAIN RESULTS
We included 120 trials (29,592 participants randomised in 116 trials; in four trials the number of randomised participants was unclear). Ninety-one studies included males and females. When reported, 72 trials included participants with mild to moderate acne, 26 included participants with severe acne, and the mean age of participants ranged from 18 to 30 years. Our included trials assessed BPO as monotherapy, as add-on treatment, or combined with other active treatments, as well as BPO of different concentrations and BPO delivered through different vehicles. Comparators included different concentrations or formulations of BPO, placebo, no treatment, or other active treatments given alone or combined. Treatment duration in 80 trials was longer than eight weeks and was only up to 12 weeks in 108 trials. Industry funded 50 trials; 63 trials did not report funding. We commonly found high or unclear risk of performance, detection, or attrition bias. Trial setting was under-reported but included hospitals, medical centres/departments, clinics, general practices, and student health centres. We reported on outcomes assessed at the end of treatment, and we classified treatment periods as short-term (two to four weeks), medium-term (five to eight weeks), or long-term (longer than eight weeks). For 'participant-reported acne improvement', BPO may be more effective than placebo or no treatment (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.12 to 1.45; 3 RCTs; 2234 participants; treatment for 10 to 12 weeks; low-certainty evidence). Based on low-certainty evidence, there may be little to no difference between BPO and adapalene (RR 0.99, 95% CI 0.90 to 1.10; 5 RCTs; 1472 participants; treatment for 11 to 12 weeks) or between BPO and clindamycin (RR 0.95, 95% CI 0.68 to 1.34; 1 RCT; 240 participants; treatment for 10 weeks) (outcome not reported for BPO versus erythromycin or salicylic acid). For 'withdrawal due to adverse effects', risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment (RR 2.13, 95% CI 1.55 to 2.93; 24 RCTs; 13,744 participants; treatment for 10 to 12 weeks; low-certainty evidence); the most common causes of withdrawal were erythema, pruritus, and skin burning. Only very low-certainty evidence was available for the following comparisons: BPO versus adapalene (RR 1.85, 95% CI 0.94 to 3.64; 11 RCTs; 3295 participants; treatment for 11 to 24 weeks; causes of withdrawal not clear), BPO versus clindamycin (RR 1.93, 95% CI 0.90 to 4.11; 8 RCTs; 3330 participants; treatment for 10 to 12 weeks; causes of withdrawal included local hypersensitivity, pruritus, erythema, face oedema, rash, and skin burning), erythromycin (RR 1.00, 95% CI 0.07 to 15.26; 1 RCT; 60 participants; treatment for 8 weeks; withdrawal due to dermatitis), and salicylic acid (no participants had adverse event-related withdrawal; 1 RCT; 59 participants; treatment for 12 weeks). There may be little to no difference between these groups in terms of withdrawal; however, we are unsure of the results because the evidence is of very low certainty. For 'proportion of participants experiencing any adverse event', very low-certainty evidence leaves us uncertain about whether BPO increased adverse events when compared with placebo or no treatment (RR 1.40, 95% CI 1.15 to 1.70; 21 RCTs; 11,028 participants; treatment for 10 to 12 weeks), with adapalene (RR 0.71, 95% CI 0.50 to 1.00; 7 RCTs; 2120 participants; treatment for 11 to 24 weeks), with erythromycin (no participants reported any adverse events; 1 RCT; 89 participants; treatment for 10 weeks), or with salicylic acid (RR 4.77, 95% CI 0.24 to 93.67; 1 RCT; 41 participants; treatment for 6 weeks). Moderate-certainty evidence shows that the risk of adverse events may be increased for BPO versus clindamycin (RR 1.24, 95% CI 0.97 to 1.58; 6 RCTs; 3018 participants; treatment for 10 to 12 weeks); however, the 95% CI indicates that BPO might make little to no difference. Most reported adverse events were mild to moderate, and local dryness, irritation, dermatitis, erythema, application site pain, and pruritus were the most common.
AUTHORS' CONCLUSIONS
Current evidence suggests that BPO as monotherapy or add-on treatment may be more effective than placebo or no treatment for improving acne, and there may be little to no difference between BPO and either adapalene or clindamycin. Our key efficacy evidence is based on participant self-assessment; trials of BPO versus erythromycin or salicylic acid did not report this outcome. For adverse effects, the evidence is very uncertain regarding BPO compared with adapalene, erythromycin, or salicylic acid. However, risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment. Withdrawal may be linked to tolerability rather than to safety. Risk of mild to moderate adverse events may be higher with BPO compared with clindamycin. Further trials should assess the comparative effects of different preparations or concentrations of BPO and combination BPO versus monotherapy. These trials should fully assess and report adverse effects and patient-reported outcomes measured on a standardised scale.
Topics: Acne Vulgaris; Adolescent; Adult; Benzoyl Peroxide; Cicatrix; Dermatologic Agents; Female; Humans; Male; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32175593
DOI: 10.1002/14651858.CD011154.pub2 -
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 -
The Cochrane Database of Systematic... Sep 2019Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA...
BACKGROUND
Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been approved by US Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect.
OBJECTIVES
To assess the effectiveness and safety of topical CsA in the treatment of dry eye.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 16 February 2018.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone.
DATA COLLECTION AND ANALYSIS
We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 30 RCTs (4009 participants) with follow-up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between-group estimates of effect or meta-analysis.Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) -4.80, 95% confidence interval (CI) -6.41 to -3.19; low-certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD -0.35, 95% CI -0.69 to -0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low-certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from -4.05 (95% CI -6.67 to -1.73) to 3.26 (95% CI -1.52 to 5.00) (low-certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low-certainty evidence). Four trials reported MD in tear film stability measured by tear break-up time at 6 months and the estimates ranged from -1.98 (95% CI -3.59 to -0.37) to 1.90 (95% CI 1.44 to 2.36) (low-certainty evidence). Three trials reported RR of improved tear break-up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low-certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low-certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta-analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow-up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low-certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment-related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low-certainty evidence).Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between-group effect estimates or meta-analyses.
AUTHORS' CONCLUSIONS
Despite the widespread use of topical CsA to treat dry eye, we found that evidence on the effect of CsA on ocular discomfort and ocular surface and tear film parameters such as corneal fluorescein staining, Schirmer's test, and TBUT is inconsistent and sometimes may not be different from vehicle or artificial tears for the time periods reported in the trials. There may be an increase in non-serious, treatment-related adverse effects (particularly burning) in the CsA group. Topical CsA may increase the number of conjunctival goblet cells. However, current evidence does not support that improvements in conjunctival mucus production (through increased conjunctival goblet cells) translate to improved symptoms or ocular surface and tear film parameters. All published trials were short term and did not assess whether CsA has longer-term disease-modifying effects. Well-planned, long-term, large clinical trials are needed to better assess CsA on long-term dry eye-modifying effects. A core outcome set, which ideally includes both biomarkers and patient-reported outcomes in the field of dry eye, is needed.
Topics: Cyclosporine; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Randomized Controlled Trials as Topic
PubMed: 31517988
DOI: 10.1002/14651858.CD010051.pub2 -
Tropical Medicine and Infectious Disease Jan 2021There is increasing evidence that human movement facilitates the global spread of resistant bacteria and antimicrobial resistance (AMR) genes. We systematically reviewed... (Review)
Review
There is increasing evidence that human movement facilitates the global spread of resistant bacteria and antimicrobial resistance (AMR) genes. We systematically reviewed the literature on the impact of travel on the dissemination of AMR. We searched the databases Medline, EMBASE and SCOPUS from database inception until the end of June 2019. Of the 3052 titles identified, 2253 articles passed the initial screening, of which 238 met the inclusion criteria. The studies covered 30,060 drug-resistant isolates from 26 identified bacterial species. Most were enteric, accounting for 65% of the identified species and 92% of all documented isolates. High-income countries were more likely to be recipient nations for AMR originating from middle- and low-income countries. The most common origin of travellers with resistant bacteria was Asia, covering 36% of the total isolates. Beta-lactams and quinolones were the most documented drug-resistant organisms, accounting for 35% and 31% of the overall drug resistance, respectively. Medical tourism was twice as likely to be associated with multidrug-resistant organisms than general travel. International travel is a vehicle for the transmission of antimicrobial resistance globally. Health systems should identify recent travellers to ensure that adequate precautions are taken.
PubMed: 33467065
DOI: 10.3390/tropicalmed6010011 -
Journal of Materials Chemistry. B Sep 2022In recent years, the efficacy of nano-drugs has not been significantly better than that of the drugs themselves, mainly because nano-drugs enter the tumor vasculature,... (Review)
Review
In recent years, the efficacy of nano-drugs has not been significantly better than that of the drugs themselves, mainly because nano-drugs enter the tumor vasculature, stay near the blood vessels, and cannot enter the tumor tissues or tumor cells to complete the drug delivery process. Although intratumor injection can significantly decrease this risk, the side effects are strong. The advent of drug delivery carrier materials offers an opportunity to avoid the side effects of systemic drug delivery and the damage caused by tumor resection, holding great promise for the future of cancer therapy. Here, we systematically review recent research advances in the classification of drug delivery carrier materials and the delivery process in drug delivery systems. This review is divided into several main sections, first, we summarize the classification of tumor drug carrier materials, including drug delivery vectors and gene delivery vectors, , which are introduced in detail, respectively. Then we describe the carrier materials to deliver the drug cascade and the transition pathways for drug delivery, including stabilization transitions, charge inversions, and size changes. Finally, we discuss the current design strategies and research progress of drug vectors and provide a summary and outlook. This review aims to summarize different drug delivery vehicles and delivery processes to provide ideas for effective cancer therapy.
Topics: Drug Carriers; Drug Delivery Systems; Gene Transfer Techniques; Genetic Therapy; Humans; Neoplasms
PubMed: 36048171
DOI: 10.1039/d2tb01326f -
International Journal of Pharmaceutics Mar 2023The pK values of functional groups is crucial in determining the pharmacokinetic properties of a drug, affecting its absorption and thus bioavailability. This... (Review)
Review
The pK values of functional groups is crucial in determining the pharmacokinetic properties of a drug, affecting its absorption and thus bioavailability. This physicochemical property is also vital for the designing of drug excipients and vehicles. There are currently 13 known methods of determining a pK value, namely: potentiometric titration, spectrometry, fluorometry, NMR, HPLC, conductometry, electrophoresis, voltammetry, solubility, partition coefficient, calorimetry, computational, and surface tension. Some of these techniques are more widely utilized and well-established compared to others, with each having their inherent advantages and disadvantages. This review discusses each of the aforementioned techniques with emphasis on their pros and cons.
Topics: Hydrogen-Ion Concentration; Fluorometry; Conductometry; Solubility
PubMed: 36858133
DOI: 10.1016/j.ijpharm.2023.122783