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The British Journal of Dermatology Nov 2022Various treatments for acne vulgaris exist, but little is known about their comparative effectiveness in relation to acne severity. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Various treatments for acne vulgaris exist, but little is known about their comparative effectiveness in relation to acne severity.
OBJECTIVES
To identify best treatments for mild-to-moderate and moderate-to-severe acne, as determined by clinician-assessed morphological features.
METHODS
We undertook a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, published up to May 2020. Outcomes included percentage change in total lesion count from baseline, treatment discontinuation for any reason, and discontinuation owing to side-effects. Risk of bias was assessed using the Cochrane risk-of-bias tool and bias adjustment models. Effects for treatments with ≥ 50 observations each compared with placebo are reported below.
RESULTS
We included 179 RCTs with approximately 35 000 observations across 49 treatment classes. For mild-to-moderate acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with benzoyl peroxide (BPO) [mean difference 26·16%, 95% credible interval (CrI) 16·75-35·36%]; physical - chemical peels, e.g. salicylic or mandelic acid (39·70%, 95% CrI 12·54-66·78%) and photochemical therapy (combined blue/red light) (35·36%, 95% CrI 17·75-53·08%). Oral pharmacological treatments (e.g. antibiotics, hormonal contraceptives) did not appear to be effective after bias adjustment. BPO and topical retinoids were less well tolerated than placebo. For moderate-to-severe acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with lincosamide (clindamycin) (44·43%, 95% CrI 29·20-60·02%); oral pharmacological - isotretinoin of total cumulative dose ≥ 120 mg kg per single course (58·09%, 95% CrI 36·99-79·29%); physical - photodynamic therapy (light therapy enhanced by a photosensitizing chemical) (40·45%, 95% CrI 26·17-54·11%); combined - BPO with topical retinoid and oral tetracycline (43·53%, 95% CrI 29·49-57·70%). Topical retinoids and oral tetracyclines were less well tolerated than placebo. The quality of included RCTs was moderate to very low, with evidence of inconsistency between direct and indirect evidence. Uncertainty in findings was high, in particular for chemical peels, photochemical therapy and photodynamic therapy. However, conclusions were robust to potential bias in the evidence.
CONCLUSIONS
Topical pharmacological treatment combinations, chemical peels and photochemical therapy were most effective for mild-to-moderate acne. Topical pharmacological treatment combinations, oral antibiotics combined with topical pharmacological treatments, oral isotretinoin and photodynamic therapy were most effective for moderate-to-severe acne. Further research is warranted for chemical peels, photochemical therapy and photodynamic therapy for which evidence was more limited. What is already known about this topic? Acne vulgaris is the eighth most common disease globally. Several topical, oral, physical and combined treatments for acne vulgaris exist. Network meta-analysis (NMA) synthesizes direct and indirect evidence and allows simultaneous inference for all treatments forming an evidence network. Previous NMAs have assessed a limited range of treatments for acne vulgaris and have not evaluated effectiveness of treatments for moderate-to-severe acne. What does this study add? For mild-to-moderate acne, topical treatment combinations, chemical peels, and photochemical therapy (combined blue/red light; blue light) are most effective. For moderate-to-severe acne, topical treatment combinations, oral antibiotics combined with topical treatments, oral isotretinoin and photodynamic therapy (light therapy enhanced by a photosensitizing chemical) are most effective. Based on these findings, along with further clinical and cost-effectiveness considerations, National Institute for Health and Care Excellence (NICE) guidance recommends, as first-line treatments, fixed topical treatment combinations for mild-to-moderate acne and fixed topical treatment combinations, or oral tetracyclines combined with topical treatments, for moderate-to-severe acne.
Topics: Humans; Isotretinoin; Network Meta-Analysis; Acne Vulgaris; Anti-Bacterial Agents; Tetracycline
PubMed: 35789996
DOI: 10.1111/bjd.21739 -
Ophthalmologica. Journal International... 2014Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal... (Review)
Review
Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal fibrosis and visual deterioration. Other ectatic corneal disorders include: post-LASIK ectasia (PLE) and pellucid marginal degeneration (PMD). Corneal crosslinking (CXL) is a procedure whereby riboflavin sensitization with ultraviolet A radiation induces stromal crosslinks. This alters corneal biomechanics, causing an increase in corneal stiffness. In recent years, CXL has been an established treatment for the arrest of KCN, PLE and PMD progression. CXL has also been shown to be effective in the treatment of corneal infections, chemical burns, bullous keratopathy and other forms of corneal edema. This is a current review of CXL - its biomechanical principles, the evolution of CXL protocols in the past, present and future, indications for treatment, treatment efficacy and safety.
Topics: Collagen; Cornea; Corneal Stroma; Cross-Linking Reagents; Elasticity; Humans; Keratoconus; Photosensitizing Agents; Riboflavin; Ultraviolet Rays
PubMed: 24751584
DOI: 10.1159/000357979 -
JAMA Dermatology Jul 2017References to the expected treatment response to phototherapy would be helpful in the management of vitiligo because phototherapy requires long treatment durations over... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
References to the expected treatment response to phototherapy would be helpful in the management of vitiligo because phototherapy requires long treatment durations over several months.
OBJECTIVE
To estimate the treatment response of vitiligo to phototherapy.
DATA SOURCES
A comprehensive database search of MEDLINE, EMBASE, and the Cochrane library from inception to January 26, 2016, was performed for all prospective studies. The main keywords used were vitiligo, phototherapy, psoralen, PUVA, ultraviolet, NBUVB, and narrowband.
STUDY SELECTION
All prospective studies reporting phototherapy outcome for at least 10 participants with generalized vitiligo were included. Of 319 studies initially identified, the full texts of 141 studies were assessed for eligibility, and 35 were finally included in the analysis. Of these, 29 studies included 1201 patients undergoing narrowband UV-B (NBUVB) phototherapy, and 9 included 227 patients undergoing psoralen-UV-A (PUVA) phototherapy.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted the following data: study design, number and characteristics of the participants, phototherapy protocol, and rate of repigmentation based on the quartile scale. Single-arm meta-analyses were performed for the NBUVB and PUVA groups. Sample size-weighted means were calculated using a random-effects model for the repigmentation rates of the included studies.
MAIN OUTCOMES AND MEASURES
The primary outcomes were at least mild (≥25%), at least moderate (≥50%), and marked (≥75%) responses on a quartile scale. Response rates were calculated as the number of participants who showed the corresponding repigmentation divided by the number of all participants enrolled in the individual studies.
RESULTS
The meta-analysis included 35 unique studies (1428 unique patients). For NBUVB phototherapy, an at least mild response occurred in 62.1% (95% CI, 46.9%-77.3%) of 130 patients in 3 studies at 3 months, 74.2% (95% CI, 68.5%-79.8%) of 232 patients in 11 studies at 6 months, and 75.0% (95% CI, 60.9%-89.2%) of 512 patients in 8 studies at 12 months. A marked response was achieved in 13.0% (95% CI, 2.1%-23.9%) of 106 patients in 2 studies at 3 months, 19.2% (95% CI, 11.4%-27.0%) of 266 patients in 13 studies at 6 months, and 35.7% (95% CI, 21.5%-49.9%) of 540 patients in 9 studies at 12 months. For PUVA phototherapy, an at least mild response occurred in 51.4% (95% CI, 28.1%-74.7%) of 103 patients in 4 studies at 6 months and 61.6% (95% CI, 20.2%-100%) of 72 patients in 3 studies at 12 months. In the subgroup analyses, marked responses were achieved on the face and neck in 44.2% (95% CI, 24.2%-64.2%), on the trunk in 26.1% (95% CI, 8.7%-43.5%), on the extremities in 17.3% (95% CI, 8.2%-26.5%), and on the hands and feet in none after at least 6 months of NBUVB phototherapy.
CONCLUSIONS AND RELEVANCE
Long-duration phototherapy should be encouraged to enhance the treatment response in vitiligo. The greatest response is anticipated on the face and neck.
Topics: Humans; PUVA Therapy; Photosensitizing Agents; Phototherapy; Skin Pigmentation; Time Factors; Treatment Outcome; Ultraviolet Therapy; Vitiligo
PubMed: 28355423
DOI: 10.1001/jamadermatol.2017.0002 -
The Cochrane Database of Systematic... Nov 2020Basal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Basal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. First-line treatment is usually surgical excision, but alternatives are available. New published studies and the development of non-surgical treatments meant an update of our Cochrane Review (first published in 2003, and previously updated in 2007) was timely.
OBJECTIVES
To assess the effects of interventions for BCC in immunocompetent adults.
SEARCH METHODS
We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions for BCC in immunocompetent adults with histologically-proven, primary BCC. Eligible comparators were placebo, active treatment, other treatments, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcome measures were recurrence at three years and five years (measured clinically) (we included recurrence data outside of these time points if there was no measurement at three or five years) and participant- and observer-rated good/excellent cosmetic outcome. Secondary outcomes included pain during and after treatment, early treatment failure within six months, and adverse effects (AEs). We used GRADE to assess evidence certainty for each outcome.
MAIN RESULTS
We included 52 RCTs (26 new) involving 6690 participants (median 89) in this update. All studies recruited from secondary care outpatient clinics. More males than females were included. Study duration ranged from six weeks to 10 years (average 13 months). Most studies (48/52) included only low-risk BCC (superficial (sBCC) and nodular (nBCC) histological subtypes). The majority of studies were at low or unclear risk of bias for most domains. Twenty-two studies were industry-funded: commercial sponsors conducted most of the studies assessing imiquimod, and just under half of the photodynamic therapy (PDT) studies. Overall, surgical interventions have the lowest recurrence rates. For high-risk facial BCC (high-risk histological subtype or located in the facial 'H-zone' or both), there may be slightly fewer recurrences with Mohs micrographic surgery (MMS) compared to surgical excision (SE) at three years (1.9% versus 2.9%, respectively) (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.16 to 2.64; 1 study, 331 participants; low-certainty evidence) and at five years (3.2% versus 5.2%, respectively) (RR 0.61, 95% CI 0.18 to 2.04; 1 study, 259 participants; low-certainty evidence). However, the 95% CI also includes the possibility of increased risk of recurrence and no difference between treatments. There may be little to no difference regarding improvement of cosmetic outcomes between MMS and SE, judged by participants and observers 18 months post-operatively (one study; low-certainty evidence); however, no raw data were available for this outcome. When comparing imiquimod and SE for nBCC or sBCC at low-risk sites, imiquimod probably results in more recurrences than SE at three years (16.4% versus 1.6%, respectively) (RR 10.30, 95% CI 3.22 to 32.94; 1 study, 401 participants; moderate-certainty evidence) and five years (17.5% versus 2.3%, respectively) (RR 7.73, 95% CI 2.81 to 21.3; 1 study, 383 participants; moderate-certainty evidence). There may be little to no difference in the number of participant-rated good/excellent cosmetic outcomes (RR 1.00, 95% CI 0.94 to 1.06; 1 study, 326 participants; low-certainty evidence). However, imiquimod may result in greater numbers of good/excellent cosmetic outcomes compared to SE when observer-rated (60.6% versus 35.6%, respectively) (RR 1.70, 95% CI 1.35 to 2.15; 1 study, 344 participants; low-certainty evidence). Both cosmetic outcomes were measured at three years. Based on one study of 347 participants with high- and low-risk primary BCC of the face, radiotherapy may result in more recurrences compared to SE under frozen section margin control at three years (5.2% versus 0%, respectively) (RR 19.11, 95% CI 1.12 to 325.78; low-certainty evidence) and at four years (6.4% versus 0.6%, respectively) (RR 11.06, 95% CI 1.44 to 84.77; low-certainty evidence). Radiotherapy probably results in a smaller number of good participant- (RR 0.76, 95% CI 0.63 to 0.91; 50.3% versus 66.1%, respectively) or observer-rated (RR 0.48, 95% CI 0.37 to 0.62; 28.9% versus 60.3%, respectively) good/excellent cosmetic outcomes compared to SE, when measured at four years, where dyspigmentation and telangiectasia can occur (both moderate-certainty evidence). Methyl-aminolevulinate (MAL)-PDT may result in more recurrences compared to SE at three years (36.4% versus 0%, respectively) (RR 26.47, 95% CI 1.63 to 429.92; 1 study; 68 participants with low-risk nBCC in the head and neck area; low-certainty evidence). There were no useable data for measurement at five years. MAL-PDT probably results in greater numbers of participant- (RR 1.18, 95% CI 1.09 to 1.27; 97.3% versus 82.5%) or observer-rated (RR 1.87, 95% CI 1.54 to 2.26; 87.1% versus 46.6%) good/excellent cosmetic outcomes at one year compared to SE (2 studies, 309 participants with low-risk nBCC and sBCC; moderate-certainty evidence). Based on moderate-certainty evidence (single low-risk sBCC), imiquimod probably results in fewer recurrences at three years compared to MAL-PDT (22.8% versus 51.6%, respectively) (RR 0.44, 95% CI 0.32 to 0.62; 277 participants) and five years (28.6% versus 68.6%, respectively) (RR 0.42, 95% CI 0.31 to 0.57; 228 participants). There is probably little to no difference in numbers of observer-rated good/excellent cosmetic outcomes at one year (RR 0.98, 95% CI 0.84 to 1.16; 370 participants). Participant-rated cosmetic outcomes were not measured for this comparison. AEs with surgical interventions include wound infections, graft necrosis and post-operative bleeding. Local AEs such as itching, weeping, pain and redness occur frequently with non-surgical interventions. Treatment-related AEs resulting in study modification or withdrawal occurred with imiquimod and MAL-PDT.
AUTHORS' CONCLUSIONS
Surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with MMS over SE for high-risk facial primary BCC (low-certainty evidence). Non-surgical treatments, when used for low-risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. Of the non-surgical treatments, imiquimod has the best evidence to support its efficacy. Overall, evidence certainty was low to moderate. Priorities for future research include core outcome measures and studies with longer-term follow-up.
Topics: Adult; Aminolevulinic Acid; Antineoplastic Agents; Carcinoma, Basal Cell; Cryotherapy; Female; Humans; Imiquimod; Immunocompetence; Laser Therapy; Male; Mohs Surgery; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Radiotherapy; Randomized Controlled Trials as Topic; Skin Neoplasms; Treatment Outcome
PubMed: 33202063
DOI: 10.1002/14651858.CD003412.pub3 -
The Cochrane Database of Systematic... Feb 2015Vitiligo is a chronic skin disorder characterised by patchy loss of skin colour. Some people experience itching before the appearance of a new patch. It affects people... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitiligo is a chronic skin disorder characterised by patchy loss of skin colour. Some people experience itching before the appearance of a new patch. It affects people of any age or ethnicity, more than half of whom develop it before the age of 20 years. There are two main types: generalised vitiligo, the common symmetrical form, and segmental, affecting only one side of the body. Around 1% of the world's population has vitiligo, a disease causing white patches on the skin. Several treatments are available. Some can restore pigment but none can cure the disease.
OBJECTIVES
To assess the effects of all therapeutic interventions used in the management of vitiligo.
SEARCH METHODS
We updated our searches of the following databases to October 2013: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2013, Issue 10), MEDLINE, Embase, AMED, PsycINFO, CINAHL and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the effects of treatments for vitiligo.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility and methodological quality, and extracted data.
MAIN RESULTS
This update of the 2010 review includes 96 studies, 57 from the previous update and 39 new studies, totalling 4512 participants. Most of the studies, covering a wide range of interventions, had fewer than 50 participants. All of the studies assessed repigmentation, however only five reported on all of our three primary outcomes which were quality of life, > 75% repigmentation and adverse effects. Of our secondary outcomes, six studies measured cessation of spread but none assessed long-term permanence of repigmentation resulting from treatment at two years follow-up.Most of the studies assessed combination therapies which generally reported better results. New interventions include seven new surgical interventions.We analysed the data from 25 studies which assessed our primary outcomes. We used the effect measures risk ratio (RR), and odds ratio (OR) with their 95% confidence intervals (CI) and where N is the number of participants in the study.We were only able to analyse one of nine studies assessing quality of life and this showed no statistically significant improvement between the comparators.Nine analyses from eight studies reported >75% repigmentation. In the following studies the repigmentation was better in the combination therapy group: calcipotriol plus PUVA (psoralen with UVA light) versus PUVA (paired OR 4.25, 95% CI 1.43 to 12.64, one study, N = 27); hydrocortisone-17-butyrate plus excimer laser versus excimer laser alone (RR 2.57, 95% CI 1.20 to 5.50, one study, N = 84); oral minipulse of prednisolone (OMP) plus NB-UVB (narrowband UVB) versus OMP alone (RR 7.41, 95% CI 1.03 to 53.26, one study, N = 47); azathioprine with PUVA versus PUVA alone (RR 17.77, 95% CI 1.08 to 291.82, one study, N = 58) and 8-Methoxypsoralen (8-MOP ) plus sunlight versus psoralen (RR 2.50, 95% CI 1.06 to 5.91, one study, N = 168). In these three studies ginkgo biloba was better than placebo (RR 4.40, 95% CI 1.08 to 17.95, one study, N = 47); clobetasol propionate was better than PUVAsol (PUVA with sunlight) (RR 4.70, 95% CI 1.14 to 19.39, one study, N = 45); split skin grafts with PUVAsol was better than minipunch grafts with PUVAsol (RR 1.89, 95% CI 1.25 to 2.85, one study, N = 64).We performed one meta-analysis of three studies, in which we found a non-significant 60% increase in the proportion of participants achieving >75% repigmentation in favour of NB-UVB compared to PUVA (RR 1.60, 95% CI 0.74 to 3.45; I² = 0%).Studies assessing topical preparations, in particular topical corticosteroids, reported most adverse effects. However, in combination studies it was difficult to ascertain which treatment caused these effects. We performed two analyses from a pooled analysis of three studies on adverse effects. Where NB-UVB was compared to PUVA, the NB-UVB group reported less observations of nausea in three studies (RR 0.13, 95% CI 0.02 to 0.69; I² = 0% three studies, N = 156) and erythema in two studies (RR 0.73, 95% CI 0.55 to 0.98; I² = 0%, two studies, N = 106), but not itching in two studies (RR 0.57, 95% CI 0.20 to 1.60; I² = 0%, two studies, N = 106).Very few studies only assessed children or included segmental vitiligo. We found one study of psychological interventions but we could not include the outcomes in our statistical analyses. We found no studies evaluating micropigmentation, depigmentation, or cosmetic camouflage.
AUTHORS' CONCLUSIONS
This review has found some evidence from individual studies to support existing therapies for vitiligo, but the usefulness of the findings is limited by the different designs and outcome measurements and lack of quality of life measures. There is a need for follow-up studies to assess permanence of repigmentation as well as high- quality randomised trials using standardised measures and which also address quality of life.
Topics: Combined Modality Therapy; Ginkgo biloba; Humans; Lasers, Excimer; PUVA Therapy; Photosensitizing Agents; Phototherapy; Plant Extracts; Quality of Life; Randomized Controlled Trials as Topic; Skin Pigmentation; Skin Transplantation; Steroids; Vitiligo
PubMed: 25710794
DOI: 10.1002/14651858.CD003263.pub5 -
The Cochrane Database of Systematic... Jun 2014Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions... (Review)
Review
BACKGROUND
Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP.
OBJECTIVES
To assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults.
SEARCH METHODS
We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014.
SELECTION CRITERIA
Randomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively.
MAIN RESULTS
We included one trial with a total of 23 participants. This study was at high risk of bias. None of our primary outcomes and only one of our secondary outcomes (reduction in volume of disease, assessed endoscopically) was measured in the study. There was no significant difference between the groups (very low-quality evidence). Adverse effects reported included airway swelling requiring intubation in a child with severe RRP a few hours after photodynamic therapy.
AUTHORS' CONCLUSIONS
There is insufficient evidence from high-quality randomised controlled trials to determine whether photodynamic therapy alters the course of disease or provides an added benefit to surgery in patients with recurrent respiratory papillomatosis. Multicentre randomised controlled trials with appropriate sample sizes and long-term follow-up are required to evaluate whether photodynamic therapy is of benefit. Outcomes such as improvement in symptoms (respiratory function and voice quality) and quality of life should be measured in future trials.
Topics: Adult; Humans; Mesoporphyrins; Papillomavirus Infections; Photochemotherapy; Photosensitizing Agents; Randomized Controlled Trials as Topic; Recurrence; Respiratory Tract Infections
PubMed: 24898010
DOI: 10.1002/14651858.CD009810.pub2 -
Vascular Pharmacology Jun 2023The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its photosensitizing properties, but... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its photosensitizing properties, but photosensitivity has also been reported for other antihypertensive drugs. We conducted a systematic review and meta-analysis to compare skin cancer risk among antihypertensive drug classes and individual blood pressure lowering drugs.
METHODS
We searched Medline, Embase, Cochrane and the Web of Science and included studies that investigated the association between antihypertensive medication exposure and non-melanoma skin cancer (NMSC) or cutaneous malignant melanoma (CMM). We combined the extracted odds ratios (OR) using a random effects model.
RESULTS
We included 42 studies with a total of 16,670,045 subjects. Diuretics, in particular hydrochlorothiazide, were examined most frequently. Only 2 studies provided information about antihypertensive co-medication. Exposure to diuretics (OR 1.27 [1.09-1.47]) and calcium channel blockers (OR 1.06 [1.04-1.09]) was associated with an increased risk for NMSC. The increased risk for NMSC was only observed in case control studies and studies that did not correct for sun exposure, skin phototype or smoking. Studies that did correct for covariates as well as cohort studies did not show a significantly increased risk for NMSC. Egger's test revealed a significant publication bias for the subgroup of diuretics, hydrochlorothiazide and case-control studies concerning NMSC (p < 0.001).
CONCLUSION
The available studies investigating the potential skin cancer risk that is associated with antihypertensive medication have significant shortcomings. Also, a significant publication bias is present. We found no increased skin cancer risk when analyzing cohort studies or studies that corrected for important covariates. (PROSPERO (CRD42020138908)).
Topics: Humans; Antihypertensive Agents; Skin Neoplasms; Hydrochlorothiazide; Melanoma; Diuretics; Hypertension
PubMed: 37084802
DOI: 10.1016/j.vph.2023.107173 -
Acta Neurochirurgica Jan 2017Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In... (Review)
Review
BACKGROUND
Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma.
METHODS
We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.
RESULTS
The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.
CONCLUSIONS
5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.
Topics: Aminolevulinic Acid; Animals; Brain Neoplasms; Fluorescent Dyes; Glioma; Humans; Neurosurgical Procedures; Photosensitizing Agents
PubMed: 27878374
DOI: 10.1007/s00701-016-3028-5 -
Acta Ophthalmologica May 2017Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal... (Meta-Analysis)
Meta-Analysis Review
Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal collagen cross-linking (CXL) in children. For this study, MEDLINE and Cochrane databases were searched for all studies examining the effects of standard, trans-epithelial or accelerated CXL protocols in patients age 18 years or younger. Primary outcomes were; uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) and secondary outcomes were; best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), central corneal thickness (CCT) and endothelial cell density (ECD). Standardized mean differences (SMD) and 95% confidence intervals were calculated, comparing baseline values with those at 6, 12 and 24 months. A total of 13 papers, published between May 2011 and December 2014 examining 490 eyes of 401 patients with a mean age of 15.25 (±1.5) years, were included in the qualitative analysis in this review. Nine papers were included in the meta-analysis, showing significant improvement in UCVA and BCVA and stable Kmax at 12 months, and stable UCVA, improved BCVA and improved Kmax at 24 months in the standard protocol group UCVA, BCVA and KMax were stable at 12 months in the trans-epithelial group. Mean refractive spherical equivalent (MRSE), CCT and ECD remained stable in both groups. In conclusion it was found that standard CXL may be effective in halting progression of keratoconus in pediatric patients at 1 year. However, larger, more long-term studies are required to ascertain its effectiveness.
Topics: Collagen; Cornea; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Ultraviolet Rays
PubMed: 27678078
DOI: 10.1111/aos.13224 -
Tomography (Ann Arbor, Mich.) Aug 2023Recent advances in tumor visualization have improved the extent of resection (EOR) of primary and secondary tumors of the central nervous system, while limiting the... (Meta-Analysis)
Meta-Analysis Review
Intraoperative Fluorophores: An Update on 5-Aminolevulinic Acid and Sodium Fluorescein in Resection of Tumors of the Central Nervous System and Metastatic Lesions-A Systematic Review and Meta-Analysis.
INTRODUCTION
Recent advances in tumor visualization have improved the extent of resection (EOR) of primary and secondary tumors of the central nervous system, while limiting the morbidity and mortality of the surgery. One area of recent interest has been the use of intraoperative fluorophores for tumor visualization such as 5-aminolevulinic acid (5-ala) and sodium fluorescein. We performed a systematic review and meta-analysis on the utility of fluorophore administration and EOR with each fluorophore to update the current literature.
METHODS
We conducted a systematic review and meta-analysis on the use of intraoperative 5-ala or fluorescein between 2021 and 2023 using the PubMed, SCOPUS, and WOS databases. The initial search yielded 8688 results. After inclusion and exclusion criteria were met, 44 studies remained for review. A meta-analysis was performed to compare the EOR between studies for each fluorophore and to compare the presence of intraoperative fluorescence by tumor type. Odds ratios (OR) were calculated for gross total resection (GTR), and two-way ANOVA tests were performed to compare rates of intraoperative fluorescence by fluorophore and tumor type.
RESULTS
In all groups except low-grade glioma, fluorescence was present after 5-ala administration; fluorescence was present for all groups after fluorescein administration. Two-way ANOVA analysis for both fluorophores demonstrated no statistically significant difference in presence of fluorescence between type of tumor resected. Meta-analysis of EOR did show a higher, but not significant, rate of GTR in the 5-ala group compared to controls (OR = 1.29, 95% CI = 0.49; 3.37). In the fluorescein group, there were statistically significant higher odds of GTR compared to the control group (OR = 2.10, 95% CI = 1.43; 3.10, I = 0%).
CONCLUSIONS
Both 5-ala and sodium fluorescein demonstrated intraoperative fluorescence among various tumor types in both cranial and spinal tumors, as well as efficacy in improving EOR. Both fluorophores merit further investigation for use in surgery of CNS tumors.
Topics: Humans; Fluorescein; Aminolevulinic Acid; Levulinic Acids; Glioma
PubMed: 37736977
DOI: 10.3390/tomography9050124