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The Annals of Otology, Rhinology, and... Apr 2021In tissue engineering, biomaterials create a 3D scaffold for cell-to-cell adhesion, proliferation and tissue formation. Because of their similarity to extracellular...
OBJECTIVE
In tissue engineering, biomaterials create a 3D scaffold for cell-to-cell adhesion, proliferation and tissue formation. Because of their similarity to extracellular matrix and architectural adaptability, nanofibers are of particular interest in tissue engineering. Electrospinning is a well-documented technique for nanofiber production for tissue engineering scaffolds. Here we present literature on the applications of electrospinning in the field of otolaryngology.
REVIEW METHODS
A PubMed database search was performed to isolate articles published about applications of electrospun nanofibers for tissue engineering in otolaryngology. Study design, size, material tested, site of application within the head and neck, and outcomes were obtained for each study.
RESULTS
Almost all data on electrospinning in otolaryngology was published in the last 6 years (84%), highlighting its novelty. A total of 25 pre-clinical studies were identified: 9 in vitro studies, 5 in vivo animal studies, and 11 combination studies. Sites of application included: tracheal reconstruction (n = 16), tympanic membrane repair (n = 3), cranial nerve regeneration (n = 3), mastoid osteogenesis (n = 1) and ear/nose chondrogenesis (n = 2).
IMPLICATIONS FOR PRACTICE
Tissue engineering is a burgeoning field, with recent innovative applications in the field of otolaryngology. Electrospun nanofibers specifically have relevant applications in the field of otolaryngology, due in part to their similarity to native extracellular matrix, with emerging areas of interest being tympanic membrane repair, cranial nerve regeneration and tracheal reconstruction.
Topics: Biocompatible Materials; Electrochemical Techniques; Humans; Materials Testing; Nanofibers; Otolaryngology; Tissue Engineering; Tissue Scaffolds
PubMed: 32975429
DOI: 10.1177/0003489420959692 -
ASAIO Journal (American Society For... Jan 2023Right ventricular injury (RVI) in the context of acute respiratory distress syndrome (ARDS) is well recognized as an important determinant risk factor of mortality.... (Meta-Analysis)
Meta-Analysis
Right Ventricular Injury Increases Mortality in Patients With Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.
Right ventricular injury (RVI) in the context of acute respiratory distress syndrome (ARDS) is well recognized as an important determinant risk factor of mortality. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is part of the algorithm for the management of patients with severe ARDS and severely impaired gas exchange. Although VV-ECMO may theoretically protect the RV it is uncertain to what degree RVI persists despite VV-ECMO support, and whether it continues to influence mortality after ECMO initiation. The aim of this systematic review and meta-analysis was to investigate the impact of RVI on mortality in this context, testing the hypothesis that RVI worsens mortality in this cohort. We performed a systematic search that identified seven studies commenting on RVI and mortality in patients with ARDS receiving VV-ECMO. The presence of RVI was associated with greater mortality overall (odds ratios [OR]: 2.72; 95% confidence intervals [CI]: 1.52-4.85; p < 0.00) and across three subgroups (RV dilatational measures: OR: 3.51; 95% CI: 1.51-8.14; p < 0.01, RV functional measures: OR: 1.84; 95% CI: 0.99-3.42; p = 0.05, RV measurements post-ECMO initiation: OR: 1.94; 95% CI: 1.01-3.72; p < 0.05). Prospective studies are needed to investigate the causal relationship between RVI and mortality in this patient group and the best management strategies to reduce mortality.
Topics: Humans; Extracorporeal Membrane Oxygenation; Respiratory Distress Syndrome; Risk Factors; Heart Ventricles; Retrospective Studies
PubMed: 36375040
DOI: 10.1097/MAT.0000000000001854 -
The Cochrane Database of Systematic... Sep 2017Genital Chlamydia trachomatis (C.trachomatis) infection may lead to pregnancy complications such as miscarriage, preterm labour, low birthweight, preterm rupture of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genital Chlamydia trachomatis (C.trachomatis) infection may lead to pregnancy complications such as miscarriage, preterm labour, low birthweight, preterm rupture of membranes, increased perinatal mortality, postpartum endometritis, chlamydial conjunctivitis and C.trachomatis pneumonia.This review supersedes a previous review on this topic.
OBJECTIVES
To establish the most efficacious and best-tolerated therapy for treatment of genital chlamydial infection in preventing maternal infection and adverse neonatal outcomes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (26 June 2017) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) as well as studies published in abstract form assessing interventions for treating genital C.trachomatis infection in pregnancy. Cluster-RCTs were also eligible for inclusion but none were identified. Quasi-randomised trials and trials using cross-over design are not eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, assessed trial quality and extracted the data using the agreed form. Data were checked for accuracy. Evidence was assessed using the GRADE approach.
MAIN RESULTS
We included 15 trials (involving 1754 women) although our meta-analyses were based on fewer numbers of studies/women. All of the included studies were undertaken in North America from 1982 to 2001. Two studies were low risk of bias in all domains, all other studies had varying risk of bias. Four other studies were excluded and one study is ongoing.Eight comparisons were included in this review; three compared antibiotic (erythromycin, clindamycin, amoxicillin) versus placebo; five compared an antibiotic versus another antibiotic (erythromycin, clindamycin, amoxicillin, azithromycin). No study reported different antibiotic regimens. Microbiological cure (primary outcome) Antibiotics versus placebo: Erythromycin (average risk ratio (RR) 2.64, 95% confidence interval (CI) 1.60 to 4.38; two trials, 495 women; I = 68%; moderate-certainty evidence), and clindamycin (RR 4.08, 95% CI 2.35 to 7.08; one trial, 85 women;low-certainty evidence) were associated with improved microbiological cure compared to a placebo control. In one very small trial comparing amoxicillin and placebo, the results were unclear, but the evidence was graded very low (RR 2.00, 95% CI 0.59 to 6.79; 15 women). One antibiotic versus another antibiotic: Amoxicillin made little or no difference in microbiological cure in comparison to erythromycin (RR 0.97, 95% CI 0.93 to 1.01; four trials, 466 women; high-certainty evidence), probably no difference compared to clindamycin (RR 0.96, 95% CI 0.89 to 1.04; one trial, 101 women; moderate-quality evidence), and evidence is very low certainty when compared to azithromycin so the effect is not certain (RR 0.89, 95% CI 0.71 to 1.12; two trials, 144 women; very low-certainty evidence). Azithromycin versus erythromycin (average RR 1.11, 95% CI 1.00 to 1.23; six trials, 374 women; I = 53%; moderate-certainty evidence) probably have similar efficacy though results appear to favour azithromycin. Clindamycin versus erythromycin (RR 1.06, 95% CI 0.97 to 1.15; two trials, 173 women; low-certainty evidence) may have similar numbers of women with a microbiological cure between groups.Evidence was downgraded for design limitations, inconsistency, and imprecision in effect estimates. Side effects of the treatment (maternal) (secondary outcome) Antibiotics versus placebo: side effects including nausea, vomiting, and abdominal pain, were reported in two studies (495 women) but there was no clear evidence whether erythromycin was associated with more side effects than placebo and a high level of heterogeneity (I = 78%) was observed (average RR 2.93, 95% CI 0.36 to 23.76). There was no clear difference in the number of women experiencing side effects when clindamycin was compared to placebo in one small study (5/41 versus 1/44) (RR 6.35, 95% CI 0.38 to 107.45, 62 women). The side effects reported were mostly gastrointestinal and also included resolving skin rashes. One antibiotic versus another antibiotic: There was no clear difference in incidence of side effects (including nausea, vomiting, diarrhoea and abdominal pain) when amoxicillin was compared to azithromycin based on data from one small study (36 women) (RR 0.56, 95% CI 0.24 to 1.31).However, amoxicillin was associated with fewer side effects compared to erythromycin with data from four trials (513 women) (RR 0.31, 95% CI 0.21 to 0.46; I = 27%). Side effects included nausea, vomiting, diarrhoea, abdominal cramping, rash, and allergic reaction.Both azithromycin (RR 0.24, 95% CI 0.17 to 0.34; six trials, 374 women) and clindamycin (RR 0.44, 95% CI 0.22 to 0.87; two trials, 183 women) were associated with a lower incidence of side effects compared to erythromycin. These side effects included nausea, vomiting, diarrhoea and abdominal cramping.One small study (101 women) reported there was no clear difference in the number of women with side effects when amoxicillin was compared with clindamycin (RR 0.57, 95% CI 0.14 to 2.26; 107 women). The side effects reported included rash and gastrointestinal complaints. Other secondary outcomes Single trials reported data on repeated infections, preterm birth, preterm rupture of membranes, perinatal mortality and low birthweight and found no clear differences between treatments.Many of this review's secondary outcomes were not reported in the included studies.
AUTHORS' CONCLUSIONS
Treatment with antibacterial agents achieves microbiological cure from C.trachomatis infection during pregnancy. There was no apparent difference between assessed agents (amoxicillin, erythromycin, clindamycin, azithromycin) in terms of efficacy (microbiological cure and repeat infection) and pregnancy complications (preterm birth, preterm rupture of membranes, low birthweight). Azithromycin and clindamycin appear to result in fewer side effects than erythromycin.All of the studies in this review were conducted in North America, which may limit the generalisability of the results. In addition, study populations may differ in low-resource settings and these results are therefore only applicable to well-resourced settings. Furthermore, the trials in this review mainly took place in the nineties and early 2000's and antibiotic resistance may have changed since then.Further well-designed studies, with appropriate sample sizes and set in a variety of settings, are required to further evaluate interventions for treating C.trachomatis infection in pregnancy and determine which agents achieve the best microbiological cure with the least side effects. Such studies could report on the outcomes listed in this review.
Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Clindamycin; Erythromycin; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic; Reproductive Tract Infections
PubMed: 28937705
DOI: 10.1002/14651858.CD010485.pub2 -
Frontiers in Plant Science 2022Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides...
Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides providing basic nutrition, they have great potential for boosting human health. The balanced consumption of vegetables is highly recommended for supplementing the human body with better nutrition density, dietary fiber, minerals, vitamins, and bioactive compounds. However, the production and quality of fresh vegetables are influenced directly or indirectly by exposure to high temperatures or heat stress (HS). A decline in quality traits and harvestable yield are the most common effects of HS among vegetable crops. Heat-induced morphological damage, such as poor vegetative growth, leaf tip burning, and rib discoloration in leafy vegetables and sunburn, decreased fruit size, fruit/pod abortion, and unfilled fruit/pods in beans, are common, often rendering vegetable cultivation unprofitable. Further studies to trace down the possible physiological and biochemical effects associated with crop failure reveal that the key factors include membrane damage, photosynthetic inhibition, oxidative stress, and damage to reproductive tissues, which may be the key factors governing heat-induced crop failure. The reproductive stage of plants has extensively been studied for HS-induced abnormalities. Plant reproduction is more sensitive to HS than the vegetative stages, and affects various reproductive processes like pollen germination, pollen load, pollen tube growth, stigma receptivity, ovule fertility and, seed filling, resulting in poorer yields. Hence, sound and robust adaptation and mitigation strategies are needed to overcome the adverse impacts of HS at the morphological, physiological, and biochemical levels to ensure the productivity and quality of vegetable crops. Physiological traits such as the stay-green trait, canopy temperature depression, cell membrane thermostability, chlorophyll fluorescence, relative water content, increased reproductive fertility, fruit numbers, and fruit size are important for developing better yielding heat-tolerant varieties/cultivars. Moreover, various molecular approaches such as omics, molecular breeding, and transgenics, have been proved to be useful in enhancing/incorporating tolerance and can be potential tools for developing heat-tolerant varieties/cultivars. Further, these approaches will provide insights into the physiological and molecular mechanisms that govern thermotolerance and pave the way for engineering "designer" vegetable crops for better health and nutritional security. Besides these approaches, agronomic methods are also important for adaptation, escape and mitigation of HS protect and improve yields.
PubMed: 35837452
DOI: 10.3389/fpls.2022.878498 -
Journal of Investigative and Clinical... Nov 2019Lichen planus is a common chronic, inflammatory, immune-mediated mucocutaneous disorder affecting the skin and mucosa. The role of mast cells in the genesis of lichen...
Lichen planus is a common chronic, inflammatory, immune-mediated mucocutaneous disorder affecting the skin and mucosa. The role of mast cells in the genesis of lichen planus has been debated. Establishing a definitive part played by mast cells and its degranulation would possibly provide a permanent, cost-effective treatment modality for oral lichen planus (OLP). This review aims to study the expression of mast cells qualitatively and quantitatively in OLP. The research questions were framed to assess the mast cell count, localization within the epithelium basement membrane zone and degranulation of mast cells. We performed a systematic search of PubMed, Medline, Cochrane and Web of Science. We found a total of 120 studies from which 12 were found suitable for the review. There is a marked increase in the number of mast cells in OLP. The mast cells were seen in increased numbers in the epithelial and connective tissue junction at areas of basement membrane disruption. There was also an increase in the degranulation of mast cells. It is evident that there is an increase in the mast cell number in lichen planus and its subsequent degranulation.
Topics: Cell Count; Connective Tissue; Epithelium; Humans; Lichen Planus, Oral; Mast Cells
PubMed: 31454180
DOI: 10.1111/jicd.12457 -
The Cochrane Database of Systematic... Nov 2017Observational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Observational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine device or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) for decreasing intrauterine adhesions (IUAs).
OBJECTIVES
To assess the effectiveness of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy, following operative hysteroscopy for treatment of female subfertility.
SEARCH METHODS
We searched the following databases from inception to June 2017: the Cochrane Gynaecology and Fertility Group Specialised Register; the Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; CINAHL and other electronic sources of trials, including trial registers, sources of unpublished literature and reference lists. We handsearched the Journal of Minimally Invasive Gynecology, and we contacted experts in the field. We also searched reference lists of appropriate papers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy in subfertile women. The primary outcome was live birth. Secondary outcomes were clinical pregnancy, miscarriage and IUAs present at second-look hysteroscopy, along with mean adhesion scores and severity of IUAs.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of evidence using the GRADE method.
MAIN RESULTS
The overall quality of the evidence was low to very low. The main limitations were serious risk of bias related to blinding of participants and personnel, indirectness and imprecision. We identified 16 RCTs comparing a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with graft versus device without graft (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) and device combined with gel versus device (one study; 120 women). The total number of participants was 1273, but data on 1133 women were available for analysis. Only two of 16 studies included 100% infertile women; in all other studies, the proportion was variable or unknown.No study reported live birth, but some (five studies) reported outcomes that were used as surrogate outcomes for live birth (term delivery or ongoing pregnancy). Anti-adhesion therapy versus placebo or no treatment following operative hysteroscopy.There was insufficient evidence to determine whether there was a difference between the use of a device or hormonal treatment compared to no treatment or placebo with respect to term delivery or ongoing pregnancy rates (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.42 to 2.12; 107 women; 2 studies; I² = 0%; very-low-quality evidence).There were fewer IUAs at second-look hysteroscopy using a device with or without hormonal treatment or hormonal treatment or barrier gels compared with no treatment or placebo (OR 0.35, 95% CI 0.21 to 0.60; 560 women; 8 studies; I² = 0%; low-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 5 to 17). Comparisons of different anti-adhesion therapies following operative hysteroscopyIt was unclear whether there was a difference between the use of a device combined with graft versus device only for the outcome of ongoing pregnancy (OR 1.48, 95% CI 0.57 to 3.83; 180 women; 3 studies; I² = 0%; low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without graft/gel or gel combined with hormonal treatment and antibiotics compared with using a device only or hormonal treatment combined with antibiotics, but the findings of this meta-analysis were affected by evidence quality (OR 0.55, 95% CI 0.36 to 0.83; 451 women; 5 studies; I² = 0%; low-quality evidence).
AUTHORS' CONCLUSIONS
Implications for clinical practiceThe quality of the evidence ranged from very low to low. The effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for researchMore research is needed to assess the comparative safety and (cost-)effectiveness of different anti-adhesion treatments compared to no treatment or other interventions for improving key reproductive outcomes in subfertile women.
Topics: Amnion; Estrogens; Female; Gels; Humans; Hysteroscopy; Infertility, Female; Intrauterine Devices; Live Birth; Pregnancy; Randomized Controlled Trials as Topic; Second-Look Surgery; Tissue Adhesions; Uterine Diseases
PubMed: 29178172
DOI: 10.1002/14651858.CD011110.pub3 -
Alzheimer's Research & Therapy Mar 2024Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid...
BACKGROUND
Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.
METHODS
Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.
RESULTS
We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.
CONCLUSIONS
These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
Topics: Male; Humans; Female; Progranulins; Frontotemporal Dementia; Intercellular Signaling Peptides and Proteins; Virulence; Mutation; Membrane Proteins; Nerve Tissue Proteins
PubMed: 38539243
DOI: 10.1186/s13195-024-01420-z -
Journal of Clinical Periodontology Jun 2019The aim of the current systematic review was to critically appraise evidence from randomized and prospective non-randomized comparative clinical trials about the... (Meta-Analysis)
Meta-Analysis
AIM
The aim of the current systematic review was to critically appraise evidence from randomized and prospective non-randomized comparative clinical trials about the efficacy of lateral bone augmentation prior to implant placement and their outcome regarding bone width gain.
MATERIALS AND METHODS
Eight databases were searched until May 2018 for randomized and prospective non-randomized comparative trials on lateral bone augmentation prior to implant placement. After elimination of duplicate studies, data extraction and risk-of-bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MD) or relative risks (RR) and their 95% CIs were performed, followed by subgroup, meta-regression and sensitivity analyses.
RESULTS
Overall, 25 trials (16 randomized/9 non-randomized) were identified, which included a total of 553 patients (42.2% male; mean age of 43.9 years). In these included studies and populations, various modalities for primary lateral bone augmentation rendered implant placement feasible. Small discrepancies were found between overall clinical and radiographic gain (pooled gains of 3.45 ± 1.18 mm versus 2.90 ± 0.83 mm, respectively), but were not statistically significant. Bone width gain was significantly inversely associated with baseline bone width (pooled effect: -0.35 mm/mm; 95% CI: -0.63 to -0.07 mm; p = 0.01). Additionally, % graft resorption was associated with patient age (36%/year, 95% CI: -0.62 to -0.11 mm; p = 0.01). The presence of xenograft added to autologous graft led to less resorption compared to autologous graft alone (MD: 1.06 mm; 95% CI: 0.21 to 1.92 mm; p = 0.01). Barrier membrane did not yield significant difference in terms of bone width gain (MD: -0.33 mm; 95% CI: -2.24 to 1.58 mm; p > 0.05) and graft resorption (MD: 0.84 mm; 95% CI: -1.42 to 3.09 mm; p > 0.05). However, the quality of evidence ranged from very low to moderate due to bias and imprecision.
CONCLUSIONS
Initially smaller bone dimensions are associated with favours larger bone width gain, which indicates that a severe lateral bone deficiency can be effectively augmented applying primary lateral bone augmentation. Both Patients' age and recipient site (maxilla or mandible) seem to influence graft resorption. The addition of a xenograft can be helpful in reducing graft resorption. Existing evidence from randomized and prospective non-randomized trials on humans indicates that lateral bone augmentation prior to implant placement can successfully increase bone width. There are some indications that patient-related, site-related, and technique-related characteristics might influence the amount of gained bone width, but the quality of evidence is for the most part hampered by the small number of existing studies and methodological limitations that might lead to bias.
Topics: Adult; Alveolar Ridge Augmentation; Bone Transplantation; Dental Implantation, Endosseous; Dental Implants; Heterografts; Humans; Mandible; Maxilla; Prospective Studies
PubMed: 30624791
DOI: 10.1111/jcpe.13052 -
The Cochrane Database of Systematic... Jul 2014Keratoconus is an ectatic (weakening) disease of the cornea, which is the clear surface at the front of the eye. Approximately 10% to 15% of patients diagnosed with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Keratoconus is an ectatic (weakening) disease of the cornea, which is the clear surface at the front of the eye. Approximately 10% to 15% of patients diagnosed with keratoconus require corneal transplantation. This may be full-thickness (penetrating) or partial-thickness (lamellar).
OBJECTIVES
To compare visual outcomes after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty for keratoconus, and to compare additional outcomes relating to factors which may contribute to poor visual outcomes (e.g. astigmatism, graft rejection and failure).
SEARCH METHODS
We searched a number of electronic databases including CENTRAL, PubMed and EMBASE without using any date or language restrictions. We last searched the electronic databases on 31 October 2013. We also handsearched the proceedings of several international ophthalmic conferences.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing the outcomes of DALK and penetrating keratoplasty in the treatment of keratoconus.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data independently. For dichotomous data (graft failure, rejection, achievement of functional vision) results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). For continuous data (postoperative best corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), keratometric astigmatism and spherical equivalent) results were expressed as mean differences (MDs) and 95% CIs.
MAIN RESULTS
We identified two completed studies, with a total of 111 participants (n = 30 and n = 81), both conducted in Iran, that met our inclusion criteria. Participants had moderate to severe keratoconus pre-operatively and were randomly allocated to receive either DALK or penetrating keratoplasty. Only one eye of each participant was treated as part of the trials. The smaller study had 12 month follow-up data for all participants. For the larger study, four DALK surgeries had to be abandoned due to technical failure and visual and refractive outcomes were not measured in these participants. Follow-up length for the remaining 77 participants ranged from 6.8 to 36.4 months, with all 77 followed for at least three months post-suture removal. Details of the randomisation procedure were unavailable for the smaller study and so sensitivity analyses were conducted to determine if the results from this study had affected the overall results of the review.Neither of the included studies reported a difference between groups on any of the measures of post-graft visual achievement, keratometric astigmatism or spherical equivalent. A single case of graft failure in a penetrating keratoplasty was reported. No postoperative graft failures were reported in the DALK group of either study.Instances of graft rejection were reported in both groups, in both studies. The majority of these cases were successfully treated with steroids. The data, which related to all cases in each study - given that the four cases that did not go ahead as planned had already technically failed without presence of rejection - showed that rejection was less likely to occur in DALK (odds ratio (OR): 0.33, 95% confidence interval (CI) 0.14 to 0.81, GRADE rating: moderate).Results of the sensitivity analysis indicated that inclusion of the Razmju 2011 study did not bias the results with regards to rejection episodes. While sensitivity analysis showed altered results with regards to failure rates, the data available from the Javadi 2010 study alone had a very wide 95% CI, suggesting an imprecise estimate. Therefore, even after removal of the Razmju 2011 data, it is still difficult to draw conclusions regarding superiority of one technique over another with regards to graft failure.DALK was unable to be completed as planned in four cases and in a further three cases, complications during dissection required further intervention. Other adverse events, of varying severity, were reported in both intervention groups with similar frequency. For both types of surgery, these included postoperative astigmatism, steroid induced ocular hypertension and persistent epithelial defects. In recipients of DALK, one participant had interface neovascularisation (a proliferation of blood vessels where the host and donor cornea come together) and one had wrinkling of Descemet's membrane, the basement membrane separating the corneal stroma from the corneal endothelium. In the penetrating keratoplasty groups, one participant required graft resuturing and one had an atonic pupil, a condition in which the pupil dilates and is non-reactive.Overall, the quality of the evidence was rated as very low to moderate, with methodological limitations, incomplete data analysis and imprecision of findings, as well as high risk of bias in several areas for both studies.
AUTHORS' CONCLUSIONS
We found no evidence to support a difference in outcomes with regards to BCVA at three months post-graft or at any of the other time points analysed (GRADE rating: very low). We also found no evidence of a difference in outcomes with regards to graft survival, final UCVA or keratometric outcomes. We found some evidence that rejection is more likely to occur following penetrating keratoplasty than DALK (GRADE rating: moderate). The small number of studies included in the review and methodological issues relating to the two, mean that the overall quality of the evidence in this review is low. There is currently insufficient evidence to determine which technique may offer better overall outcomes - final visual acuity and time to attain this, keratometric stabilisation, risk of rejection or failure, or both, and risk of other adverse events - for patients with keratoconus. Large randomised trials comparing the outcomes of penetrating keratoplasty and DALK in the treatment of keratoconus are needed.
Topics: Corneal Transplantation; Graft Rejection; Humans; Keratoconus; Keratoplasty, Penetrating; Randomized Controlled Trials as Topic; Steroids
PubMed: 25055058
DOI: 10.1002/14651858.CD009700.pub2 -
The Cochrane Database of Systematic... Aug 2020Chronic suppurative otitis media (CSOM) is a chronic inflammation and often polymicrobial infection of the middle ear and mastoid cavity, characterised by ear discharge... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic suppurative otitis media (CSOM) is a chronic inflammation and often polymicrobial infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Topical antibiotics act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be used alone or in addition to other treatments for CSOM, such as steroids, antiseptics or ear cleaning (aural toileting). Antibiotics are commonly prescribed in combined preparations with steroids.
OBJECTIVES
To assess the effects of adding a topical steroid to topical antibiotics in the treatment of people with chronic suppurative otitis media (CSOM).
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with at least a one-week follow-up involving participants (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. The interventions were any combination of a topical antibiotic agent(s) of any class and a topical corticosteroid (steroid) of any class, applied directly into the ear canal as ear drops, powders or irrigations, or as part of an aural toileting procedure. The two main comparisons were topical antibiotic and steroid compared to a) placebo or no intervention and b) another topical antibiotic.
DATA COLLECTION AND ANALYSIS
We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks and after four weeks; health-related quality of life; ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity.
MAIN RESULTS
We included 17 studies addressing 11 treatment comparisons. A total of 1901 participants were included, with one study (40 ears) not reporting the number of participants recruited, which we therefore could not account for. No studies reported health-related quality of life. The main comparisons were: 1. Topical antibiotics with steroids versus placebo or no treatment Three studies (210 participants) compared a topical antibiotic-steroid to saline or no treatment. Resolution of discharge was not reported at between one to two weeks. One study (50 'high-risk' children) reported results at more than four weeks by ear and we could not adjust the results to by person. The study reported that 58% (of 41 ears) resolved with topical antibiotics compared with 50% (of 26 ears) with no treatment, but the evidence is very uncertain. One study (123 participants) noted minor side effects in 16% of participants in both the intervention and placebo groups (very low-certainty evidence). One study (123 participants) reported no change in bone-conduction hearing thresholds and reported no difference in tinnitus or balance problems between groups (very low-certainty evidence). One study (50 participants) reported serious complications, but it was not clear which group these patients were from, or whether the complications occurred pre- or post-treatment. One study (123 participants) reported that no side effects occurred in any participants (very low-certainty evidence). 2. Topical antibiotics with steroids versus topical antibiotics (same antibiotics) only Four studies (475 participants) were included in this comparison. Three studies (340 participants) compared topical antibiotic-steroid combinations to topical antibiotics alone. The evidence suggests little or no difference in resolution of discharge at one to two weeks: 82.7% versus 76.6% (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.96 to 1.21; 335 participants; 3 studies (4 study arms); low-certainty evidence). No results for resolution of discharge after four weeks were reported. One study (110 participants) reported local itchiness but as there was only one episode in each group it is uncertain whether there is a difference (very low-certainty evidence). Three studies (395 participants) investigated suspected ototoxicity but it was not possible to determine whether there were differences between the groups for this outcome (very low-certainty evidence). No study reported serious complications. 3. Topical antibiotics with steroids compared to topical antibiotics alone (different antibiotics) Nine studies (981 participants plus 40 ears) evaluated a range of comparisons of topical non-quinolone antibiotic-steroid combinations versus topical quinolone antibiotics alone. Resolution of discharge may be greater with quinolone topical antibiotics alone at between one to two weeks compared with non-quinolone topical antibiotics with steroids: 82.1% versus 63.2% (RR 0.77, 95% CI 0.71 to 0.84; 7 studies; 903 participants, low-certainty evidence). Results for resolution of ear discharge after four weeks were not reported. One study (52 participants) reported usable data on ear pain, two studies (419 participants) reported hearing outcomes and one study (52 participants) reported balance problems. It was not possible to determine whether there were significant differences between the groups for these outcomes (very low-certainty evidence). Two studies (149 participants) reported no serious complications (very low-certainty evidence).
AUTHORS' CONCLUSIONS
We are uncertain about the effectiveness of topical antibiotics with steroids in improving the resolution of ear discharge in patients with CSOM because of the limited amount of low-certainty evidence available. Amongst this uncertainty, we found no evidence that the addition of steroids to topical antibiotics affects the resolution of ear discharge. There is also low-certainty evidence that some types of topical antibiotics (without steroids) may be better than topical antibiotic/steroid combinations in improving resolution of discharge. There is also uncertainty about the relative effectiveness of different types of antibiotics; it is not possible to determine with any certainty whether or not quinolones are better or worse than aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.
PubMed: 35659673
DOI: 10.1002/14651858.CD013054.pub2