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The Cochrane Database of Systematic... Dec 2018Non-infectious uveitis describes a heterogenous group of ocular disorders characterised by intraocular inflammation in the absence of infection. Uveitis is a leading...
BACKGROUND
Non-infectious uveitis describes a heterogenous group of ocular disorders characterised by intraocular inflammation in the absence of infection. Uveitis is a leading cause of visual loss, most commonly due to uveitic macular oedema (UMO). Treatment is aimed at reducing disease activity by suppression of the intraocular inflammatory response. In the case of macular oedema, the aim is to restore macular architecture as quickly as possible, in order to prevent irreversible photoreceptor damage in this area. Acute exacerbations are typically managed with corticosteroids, which may be administered topically, locally or systemically. Whilst these are often rapidly effective in achieving disease control, long-term use is associated with significant local and systemic side effects, and 'steroid sparing agents' are typically used to achieve prolonged control in severe or recalcitrant disease. Anti-tumour necrosis factor (TNF) drugs block a critical cytokine in the inflammatory signalling process, and have emerged as effective steroid-sparing immunomodulatory agents in a wide range of non-ocular conditions. There is mechanistic data to suggest that they may provide a more targeted approach to disease control in UMO than other agents, but to date, these agents have predominantly been used 'off label' as the majority are not licensed for ocular use. This review aims to summarise the available literature reporting the use of anti-TNF therapy in UMO, thus developing the evidence-base on which to make future treatment decisions and develop clinical guidelines in this area.
OBJECTIVES
To assess the efficacy of anti-TNF therapy in treatment of UMO.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; LILACS; Web of Science Conference Proceedings Citation Index- Science (CPCI-S); System for Information on Grey Literature in Europe (OpenGrey); the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 29 March 2018.
SELECTION CRITERIA
We planned to include all relevant randomised controlled trials assessing the use of anti-TNF agents in treatment of UMO. No limits were applied to participant age, gender or ethnicity. The primary comparisons of this review were: anti-TNF versus no treatment or placebo; anti-TNF versus another pharmacological agent; comparison of different anti-TNF drugs; comparison of different doses and routes of administration of the same anti-TNF drug. The primary outcome measure that we assessed for this review was best-corrected visual acuity (BCVA) in the treated eye. Secondary outcome measures were anatomical macular change, clinical estimation of vitreous haze and health-related quality of life.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts retrieved through the database searches. We retrieved full-text reports of studies categorised as 'unsure' or 'include' after we had reviewed the abstracts. Two review authors independently reviewed each full-text report for eligibility. We resolved discrepancies through discussion.
MAIN RESULTS
We identified no completed or ongoing trial that was eligible for this Cochrane Review.
AUTHORS' CONCLUSIONS
Our review did not identify any evidence from randomised controlled trials for or against the role of anti-TNF agents in the management of UMO. Although there are a number of high-quality randomised controlled trials that demonstrate the efficacy of anti-TNF agents in preventing recurrence of inflammation in uveitis, the reported study outcomes do not include changes in UMO. As a result, there were insufficient data to conclude whether there was a significant treatment effect specifically for UMO. Future trials should be designed to include quantitative measures of UMO as primary study outcomes, for example by reporting the presence or absence of UMO, or by measuring central macular thickness for study participants. Furthermore, whilst UMO is an important complication of uveitis, we acknowledge that uveitis is associated with many significant structural and functional complications. It is not possible to determine treatment efficacy based on a single outcome measure. We recommend that future reviews of therapeutic interventions in uveitis should use composite measures of treatment response comprising a range of potential complications of disease.
Topics: Humans; Macular Edema; Off-Label Use; Tumor Necrosis Factor-alpha; Uveitis
PubMed: 30562409
DOI: 10.1002/14651858.CD012577.pub2 -
The Cochrane Database of Systematic... Oct 2018Diabetic macular oedema (DMO) is a complication of diabetic retinopathy and one of the most common causes of visual impairment in people with diabetes. Clinically... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic macular oedema (DMO) is a complication of diabetic retinopathy and one of the most common causes of visual impairment in people with diabetes. Clinically significant macular oedema (CSMO) is the most severe form of DMO. Intravitreal antiangiogenic therapy is now the standard treatment for DMO involving the centre of the macula, but laser photocoagulation is still used in milder or non-central DMO.
OBJECTIVES
To access the efficacy and safety of laser photocoagulation as monotherapy in the treatment of diabetic macular oedema.
SEARCH METHODS
We searched CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; MEDLINE; Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 24 July 2018.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing any type of focal/grid macular laser photocoagulation versus another type or technique of laser treatment and no intervention. We did not compare laser versus other interventions as these are covered by other Cochrane Reviews.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were gain or loss of 3 lines (0.3 logMAR or 15 ETDRS letters) of best-corrected visual acuity (BCVA) at one year of follow-up (plus or minus six months) after treatment initiation. Secondary outcomes included final or mean change in BCVA, resolution of macular oedema, central retinal thickness, quality of life and adverse events, all at one year. We graded the certainty of the evidence for each outcome using the GRADE approach.
MAIN RESULTS
We identified 24 studies (4422 eyes). The trials were conducted in Europe (nine studies), USA (seven), Asia (four) and, Africa (one), Latin America (one), Europe-Asian (one) and Oceania (one). The methodological quality of the studies was difficult to assess as they were poorly reported, so the predominant classification of bias was unclear.At one year, people with DMO receiving laser were less likely to lose BCVA compared with no intervention (risk ratio (RR) 0.42, 95% confidence interval (CI) 0.20 to 0.90; 3703 eyes; 4 studies; I = 71%; moderate-certainty evidence). There were also favourable effects observed at two and three years. One study (350 eyes) reported on partial or complete resolution of clinically significant DMO and found moderate-certainty evidence of a benefit at three years with photocoagulation (RR 1.55, 95% CI 1.30 to 1.86). Data on visual improvement, final BCVA, central macular thickness and quality of life were not available. One study related minor adverse effects on the central visual field and another reported one case of iatrogenic premacular fibrosis.Nine studies compared subthreshold versus standard macular photocoagulation (517 eyes). Subthreshold treatment was achieved with different methods of photocoagulation: non-visible conventional (two studies), micropulse (four) or nanopulse (one).Only one small study (29 eyes) reported on improvement or worsening of BCVA and estimates were very imprecise (improvement: RR 0.31, 95% CI 0.01 to 7.09; worsening: RR 0.93, 95% CI 0.15 to 5.76; very low-certainty evidence). All studies reported on continuous BCVA at one year; there was low-certainty evidence of no important difference between subthreshold and standard photocoagulation (mean difference (MD) in logMAR BCVA -0.02, 95% CI -0.07 to 0.03; 385 eyes; 7 studies; I = 42%), and were possibly different for different techniques (P = 0.07 and I = 61.5% for subgroup heterogeneity), with better results achieved with micropulse photocoagulation (MD -0.08 logMAR, 95% CI -0.16 to 0.0) as compared to the results achieved with nanopulse (MD 0.0 logMAR, 95% CI -0.06 to 0.06) and non-visible conventional (MD 0.04 logMAR, 95% CI -0.03 to 0.11), all of them compared to the standard lasers. One study reported partial to complete resolution of macular oedema at one year. There was low-certainty evidence of some benefit with standard photocoagulation, but estimates of effect were imprecise (RR 0.47, 95% CI 0.21 to 1.03; 29 eyes; 1 study). Studies also reported on the change in central macular thickness at one year and found moderate-certainty evidence of no important difference between subthreshold and standard photocoagulation (MD -9.1 μm, 95% CI -26.2 to 8.0; 385 eyes; 7 studies; I = 0%). There were no important adverse effects recorded in the studies.Nine studies compared argon laser versus another type of laser (997 eyes). There was moderate-certainty evidence of a small reduction or no difference between the interventions, with respect to improvement (RR 0.87, 95% CI 0.62 to 1.22; 773 eyes; 6 studies) and worsening of BCVA (RR 0.83, 95% CI 0.57 to 1.21; 773 eyes; 6 studies). Three studies reported few cases of subretinal fibrosis and neovascularization with argon laser and one study found subretinal fibrosis in the krypton group.One study (323 eyes) compared the modified ETDRS (mETDRS) grid technique with the mild macular grid (MMG), which uses mild, widely spaced burns throughout the macula. There was low-certainty evidence of an increased chance of visual improvement with MMG, but the estimate was imprecisely measured and the CIs include an increased risk or decreased risk of visual improvement at one year (RR 1.43, 95% CI 0.56 to 3.65; visual worsening: RR 1.40, 95% CI 0.64 to 3.05; change of logMAR visual acuity: MD -0.04 logMAR, 95% CI -0.01 to 0.09). There was a more significant reduction of central macular thickness with the mETDRS compared to the MMG technique (MD -34.0 µm, -59.8 to -8.3) in the MMG group. The study did not record important adverse effects.
AUTHORS' CONCLUSIONS
Laser photocoagulation reduces the chances of visual loss and increases those of partial to complete resolution of DMO compared to no intervention at one to three years. Subthreshold photocoagulation, particularly the micropulse technique, may be as effective as standard photocoagulation and RCTs are ongoing to assess whether this minimally invasive technique is preferable to treat milder or non-central cases of DMO.
Topics: Diabetic Retinopathy; Humans; Laser Coagulation; Lasers, Gas; Macular Edema; Randomized Controlled Trials as Topic; Treatment Outcome; Visual Acuity
PubMed: 30320466
DOI: 10.1002/14651858.CD010859.pub2 -
PloS One 2018To compare dorsal penile nerve block (DPNB) and eutectic mixture of local anesthetics (EMLA) cream for pain relief in infants during circumcision. (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To compare dorsal penile nerve block (DPNB) and eutectic mixture of local anesthetics (EMLA) cream for pain relief in infants during circumcision.
METHODS
We systematically searched Medline via PubMed, Embase, CNKI and the Cochrane Library Center Register to identify randomized controlled trials up to March 2018. Effect estimates were performed in random effect models. Mean neonate infant pain scale (NIPS) scores, incidence of hematoma, edema and erythema, mean heart rate were conducted to assessed the effect of analgesia. We found that the EMLA had significantly higher pain scores compared to DPNB (SMD = 3.72, 95% CI 1.27-6.17, P = 0.003). In DPNB group, the incidence of hematoma was significantly higher than EMLA group, OR = 0.03, 95% CI 0.00-0.24, P = 0.001. The analysis did not show any significant differences in mean heart rate and the risk of edema and erythema between EMLA and DPNB group (SMD = 21.71, 95% CI = -0.88-44.30, P = 0.06 & OR = 0.40, 95% CI 0.15-1.07, P = 0.07 & OR = 7.33, 95% CI 0.84-64.07, P = 0.07).
CONCLUSION
Based on the pooled results from the included studies, we found that DPNB was significantly more effective in pain relief as indicated by mean NIPS score than EMLA in infants during circumcision. However, use of DPNB significantly increased the risk of hematoma.
Topics: Administration, Topical; Anesthetics; Circumcision, Male; Humans; Infant; Infant, Newborn; Male; Nerve Block; Pain; Pain Management; Randomized Controlled Trials as Topic; Skin Cream
PubMed: 30188927
DOI: 10.1371/journal.pone.0203439 -
BMJ Open Jul 2018To summarise available data on the risk factors, complications and the factors associated with complications of lower limb cellulitis in Africa.
OBJECTIVE
To summarise available data on the risk factors, complications and the factors associated with complications of lower limb cellulitis in Africa.
METHODS
We did electronic searches on PubMed, EMBASE, Scopus and African Journals Online from 1 January 1986 to 30 October 2017, extracted and summarised data on the risk factors, complications and the factors associated with the complications of lower limb cellulitis from eligible literature.
RESULTS
A total of seven studies were retained for final review after the search and screening processes. Local risk factors of cellulitis reported were: disruption of the skin barrier, neglected wounds, toe-web intertrigo, leg ulcers, use of depigmentation drugs and leg oedema. Obesity was the only reported general risk factor of cellulitis. Five studies reported on the complications of cellulitis which included: abscess formation, necrotising fasciitis, bullae, haemorrhagic lesions, necrosis, phlebitis and amputations. Nicotine addiction, chronic use of non-steroidal anti-inflammatory drugs, delay in the initiation of antibiotic treatment and elevated erythrocyte sedimentation rate were risk factors of complications of lower limb cellulitis identified from three studies.
CONCLUSION
This review highlights the important role of local risk factors in the pathogenesis of lower limb cellulitis in Africa. The association between voluntary skin depigmentation and lower limb cellulitis should alert public health authorities and the general population to the health risks associated with this practice. The identification and improved management of the risk factors of lower limb cellulitis and its complications could go a long way in decreasing the morbidity and health costs incurred by lower limb cellulitis in Africa.
Topics: Africa; Cellulitis; Humans; Lower Extremity; Risk Factors
PubMed: 30037869
DOI: 10.1136/bmjopen-2017-021175 -
Ultrasound in Obstetrics & Gynecology :... Nov 2018To explore the outcome of fetuses affected by congenital parvovirus B19 (PB19) infection, with or without signs of hydrops on ultrasound. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the outcome of fetuses affected by congenital parvovirus B19 (PB19) infection, with or without signs of hydrops on ultrasound.
METHODS
PubMed, EMBASE and CINAHL databases were searched for studies reporting on prenatal diagnosis and outcome of fetal PB19 infection. The outcomes explored were miscarriage, perinatal death (PND), intrauterine death, neonatal death, spontaneous resolution of hydrops or fetal anemia, need for intrauterine transfusion (IUT), resolution of hydrops or anemia after transfusion, fetal loss following transfusion, abnormal brain scan after birth and abnormal neurodevelopmental outcome. Outcomes were reported according to the presence or absence of signs of hydrops on ultrasound. A subgroup analysis was performed including hydropic and non-hydropic fetuses diagnosed at < 20 weeks and ≥ 20 weeks of gestation. Meta-analyses of proportions and meta-analyses using individual-data random-effects logistic regression were performed to analyze the data.
RESULTS
Thirty-five observational studies were included, involving 611 fetuses affected by PB19 infection. The risks of miscarriage (odds ratio (OR), 11.5; 95% CI, 2.7-49.7) and PND (OR, 4.2; 95% CI, 1.6-11.0) were higher in fetuses with PB19 infection presenting, compared with those not presenting, signs of hydrops on ultrasound. In fetuses affected by hydrops, spontaneous resolution of the infection, defined as disappearance of hydrops without need for IUT, occurred in 5.2% (95% CI, 2.5-8.8%) of cases whereas, in the group of fetuses not affected by hydrops, infection resolved in 49.6% (95% CI, 20.7-78.6%) of cases. IUT was performed in 78.7% (95% CI, 66.4-88.8%) of hydropic and in 29.6% (95% CI, 6.0-61.6%) of non-hydropic fetuses affected by congenital PB19 infection and resolution of the infection after IUT occurred in 55.1% (95% CI, 34.0-75.3%) and in 100% (95% CI, 57.3-100%) of cases, respectively. The risk of fetal loss after IUT was higher in fetuses affected compared with those not affected by hydrops (OR, 9.8; 95% CI, 2.8-34.6). The prevalence of abnormal brain imaging was 9.8% (95% CI, 2.5-21.0%) in fetuses affected and 0.0% (95% CI, 0.0-7.0%) in those not affected by hydrops, whilst the corresponding figures for abnormal neurodevelopmental outcome were 9.5% (95% CI, 2.6-20.2) and 0.0% (95% CI, 0.0-7.5), respectively; however, statistical power to assess these outcomes was inadequate due to the small number of included cases.
CONCLUSIONS
Hydrops is the main determinant of mortality and adverse perinatal outcome in fetuses with PB19 infection. Perinatal outcome in non-hydropic fetuses is generally favorable. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Erythema Infectiosum; Female; Fetal Death; Gestational Age; Humans; Hydrops Fetalis; Parvovirus B19, Human; Pregnancy; Pregnancy Complications, Infectious; Prenatal Diagnosis
PubMed: 29785793
DOI: 10.1002/uog.19092 -
The Cochrane Database of Systematic... Apr 2018The combination of steroid and anti-vascular endothelial growth factor (VEGF) intravitreal therapeutic agents could potentially have synergistic effects for treating... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The combination of steroid and anti-vascular endothelial growth factor (VEGF) intravitreal therapeutic agents could potentially have synergistic effects for treating diabetic macular oedema (DMO). On the one hand, if combined treatment is more effective than monotherapy, there would be significant implications for improving patient outcomes. Conversely, if there is no added benefit of combination therapy, then people could be potentially exposed to unnecessary local or systemic side effects.
OBJECTIVES
To assess the effects of intravitreal agents that block vascular endothelial growth factor activity (anti-VEGF agents) plus intravitreal steroids versus monotherapy with macular laser, intravitreal steroids or intravitreal anti-VEGF agents for managing DMO.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 1); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 21 February 2018.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of intravitreal anti-VEGF combined with intravitreal steroids versus intravitreal anti-VEGF alone, intravitreal steroids alone or macular laser alone for managing DMO. We included people with DMO of all ages and both sexes. We also included trials where both eyes from one participant received different treatments.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane.Two authors independently reviewed all the titles and abstracts identified from the electronic and manual searches against the inclusion criteria. Our primary outcome was change in best corrected visual acuity (BCVA) between baseline and one year. Secondary outcomes included change in central macular thickness (CMT), economic data and quality of life. We considered adverse effects including intraocular inflammation, raised intraocular pressure (IOP) and development of cataract.
MAIN RESULTS
There were eight RCTs (703 participants, 817 eyes) that met our inclusion criteria with only three studies reporting outcomes at one year. The studies took place in Iran (3), USA (2), Brazil (1), Czech Republic (1) and South Korea (1). Seven studies used the unlicensed anti-VEGF agent bevacizumab and one study used licensed ranibizumab. The study that used licensed ranibizumab had a unique design compared with the other studies in that included eyes had persisting DMO after anti-VEGF monotherapy and received three monthly doses of ranibizumab prior to allocation. The anti-VEGF agent was combined with intravitreal triamcinolone in six studies and with an intravitreal dexamethasone implant in two studies. The comparator group was anti-VEGF alone in all studies; two studies had an additional steroid monotherapy arm, another study had an additional macular laser photocoagulation arm. Whilst we judged these studies to be at low risk of bias for most domains, at least one domain was at unclear risk in all studies.When comparing anti-VEGF/steroid with anti-VEGF monotherapy as primary therapy for DMO, we found no meaningful clinical difference in change in BCVA (mean difference (MD) -2.29 visual acuity (VA) letters, 95% confidence interval (CI) -6.03 to 1.45; 3 RCTs; 188 eyes; low-certainty evidence) or change in CMT (MD 0.20 μm, 95% CI -37.14 to 37.53; 3 RCTs; 188 eyes; low-certainty evidence) at one year. There was very low-certainty evidence on intraocular inflammation from 8 studies, with one event in the anti-VEGF/steroid group (313 eyes) and two events in the anti-VEGF group (322 eyes). There was a greater risk of raised IOP (Peto odds ratio (OR) 8.13, 95% CI 4.67 to 14.16; 635 eyes; 8 RCTs; moderate-certainty evidence) and development of cataract (Peto OR 7.49, 95% CI 2.87 to 19.60; 635 eyes; 8 RCTs; moderate-certainty evidence) in eyes receiving anti-VEGF/steroid compared with anti-VEGF monotherapy. There was low-certainty evidence from one study of an increased risk of systemic adverse events in the anti-VEGF/steroid group compared with the anti-VEGF alone group (Peto OR 1.32, 95% CI 0.61 to 2.86; 103 eyes).One study compared anti-VEGF/steroid versus macular laser therapy. At one year investigators did not report a meaningful difference between the groups in change in BCVA (MD 4.00 VA letters 95% CI -2.70 to 10.70; 80 eyes; low-certainty evidence) or change in CMT (MD -16.00 μm, 95% CI -68.93 to 36.93; 80 eyes; low-certainty evidence). There was very low-certainty evidence suggesting an increased risk of cataract in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 4.58, 95% 0.99 to 21.10, 100 eyes) and an increased risk of elevated IOP in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 9.49, 95% CI 2.86 to 31.51; 100 eyes).One study provided very low-certainty evidence comparing anti-VEGF/steroid versus steroid monotherapy at one year. There was no evidence of a meaningful difference in BCVA between treatments at one year (MD 0 VA letters, 95% CI -6.1 to 6.1, low-certainty evidence). Likewise, there was no meaningful difference in the mean CMT at one year (MD - 9 μm, 95% CI -39.87μm to 21.87μm between the anti-VEGF/steroid group and the steroid group. There was very low-certainty evidence on raised IOP at one year comparing the anti-VEGF/steroid versus steroid groups (Peto OR 0.75, 95% CI 0.16 to 3.55).No included study reported impact of treatment on patients' quality of life or economic data. None of the studies reported any cases of endophthalmitis.
AUTHORS' CONCLUSIONS
Combination of intravitreal anti-VEGF plus intravitreal steroids does not appear to offer additional visual benefit compared with monotherapy for DMO; at present the evidence for this is of low-certainty. There was an increased rate of cataract development and raised intraocular pressure in eyes treated with anti-VEGF plus steroid versus anti-VEGF alone. Patients were exposed to potential side effects of both these agents without reported additional benefit. The majority of the evidence comes from studies of bevacizumab and triamcinolone used as primary therapy for DMO. There is limited evidence from studies using licensed intravitreal anti-VEGF agents plus licensed intravitreal steroid implants with at least one year follow-up. It is not known whether treatment response is different in eyes that are phakic and pseudophakic at baseline.
Topics: Bevacizumab; Dexamethasone; Diabetic Retinopathy; Drug Therapy, Combination; Glucocorticoids; Humans; Intraocular Pressure; Intravitreal Injections; Macula Lutea; Macular Edema; Randomized Controlled Trials as Topic; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Triamcinolone; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 29669176
DOI: 10.1002/14651858.CD011599.pub2 -
Seizure Feb 2018Although the majority of adult epilepsy patients respond well to the current antiepileptic drug treatment, 20-40% of them are drug-resistant. In these patients,... (Review)
Review
PURPOSE
Although the majority of adult epilepsy patients respond well to the current antiepileptic drug treatment, 20-40% of them are drug-resistant. In these patients, resective epilepsy surgery is a curative treatment option, for which, however, only a limited number of patients is eligible. The purpose is to summarize the outcome of radiotherapy for drug-resistant non-neoplastic focal epilepsy and to elucidate its efficacy for seizure outcome and long-term toxicity in adults.
METHOD
A systematic literature search was performed in Pubmed, Ovid Medline, Cochrane library, Embase and Web of Science. The methodological quality was evaluated using an adapted QUADAS checklist.
RESULTS
Sixteen out of 170 initially identified studies were included in this systematic literature study (n = 170 patients). Twelve of the 16 studies described a positive effect of radiotherapy on seizure frequency reduction, with 98 of the patients (on average 58%, range 25%-95%) reporting no or rare seizures (defined as radiotherapy-adapted Engel class [RAEC] I and II. In total, 20% (34 patients) of the patients needed subsequent surgery due to radionecrosis, cysts formation, edema, and intracranial hypertension or remaining seizures. A dose-effect model was fitted to the available response data in an attempt to derive a relationship between prescribed dose and RAEC frequency.
CONCLUSIONS
Radiotherapy is a possible non-invasive treatment option for patients with drug-resistant focal non-neoplastic epilepsy. This systematic review showed that there is only level 4 evidence of primary radiotherapy reducing seizure frequency in adult patients. Prospective randomized trials are needed to determine its exact value compared to other treatment approaches.
Topics: Adult; Drug Resistant Epilepsy; Epilepsies, Partial; Humans; Radiosurgery; Treatment Outcome
PubMed: 29414140
DOI: 10.1016/j.seizure.2018.01.009 -
The Cochrane Database of Systematic... Nov 2017Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is characterised by hypertension and multisystem organ involvement and which has significant maternal... (Review)
Review
BACKGROUND
Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is characterised by hypertension and multisystem organ involvement and which has significant maternal and fetal morbidity and mortality. Failure of the placental vascular remodelling and reduced uteroplacental flow form the etiopathological basis of pre-eclampsia. There are several established therapies for pre-eclampsia including antihypertensives and anticonvulsants. Most of these therapies aim at controlling the blood pressure or preventing complications of elevated blood pressure, or both. Epidural therapy aims at blocking the vasomotor tone of the arteries, thereby increasing uteroplacental blood flow. This review was aimed at evaluating the available evidence about the possible benefits and risks of epidural therapy in the management of severe pre-eclampsia, to define the current evidence level of this therapy, and to determine what (if any) further evidence is required.
OBJECTIVES
To assess the effectiveness, safety and cost of the extended use of epidural therapy for treating severe pre-eclampsia in non-labouring women. This review aims to compare the use of extended epidural therapy with other methods, which include intravenous magnesium sulphate, anticonvulsants other than magnesium sulphate, with or without use of the antihypertensive drugs and adjuncts in the treatment of severe pre-eclampsia.This review only considered the use of epidural anaesthesia in the management of severe pre-eclampsia in the antepartum period and not as pain relief in labour.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (13 July 2017) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing epidural therapy versus traditional therapy for pre-eclampsia in the form of antihypertensives, anticonvulsants, magnesium sulphate, low-dose dopamine, corticosteroids or a combination of these, were eligible for inclusion. Trials using a cluster design, and studies published in abstract form only are also eligible for inclusion in this review. Cross-over trials were not eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed trials for inclusion and trial quality. There were no relevant data available for extraction.
MAIN RESULTS
We included one small study (involving 24 women). The study was a single-centre randomised trial conducted in Mexico. This study compared a control group who received antihypertensive therapy, anticonvulsant therapy, plasma expanders, corticosteroids and dypyridamole with an intervention group that received epidural block instead of the antihypertensives, as well as all the other four drugs. Lumbar epidural block was given using 0.25% bupivacaine, 10 mg bolus and 5 mg each hour on continuous epidural infusion for six hours. This study was at low risk of bias in three domains but was assessed to be high risk of bias in two domains due to lack of allocation concealment and blinding of women and staff, and unclear for random sequence generation and outcome assessor blinding.The included study did not report on any of this review's important outcomes. Meta-analysis was not possible.For the mother, these were: maternal death (death during pregnancy or up to 42 days after the end of the pregnancy, or death more than 42 days after the end of the pregnancy); development of eclampsia or recurrence of seizures; stroke; any serious morbidity: defined as at least one of stroke, kidney failure, liver failure, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, pulmonary oedema.For the baby, these were: death: stillbirths (death in utero at or after 20 weeks' gestation), perinatal deaths (stillbirths plus deaths in the first week of life), death before discharge from the hospital, neonatal deaths (death within the first 28 days after birth), deaths after the first 28 days; preterm birth (defined as the birth before 37 completed weeks' gestation); and side effects of the intervention. Reported outcomesThe included study only reported on a single secondary outcome of interest to this review: the Apgar score of the baby at birth and after five minutes and there was no clear difference between the intervention and control groups.The included study also reported a reduction in maternal diastolic arterial pressure. However, the change in maternal mean arterial pressure and systolic arterial pressure, which were the other reported outcomes of this trial, were not significantly different between the two groups.
AUTHORS' CONCLUSIONS
Currently, there is insufficient evidence from randomised controlled trials to evaluate the effectiveness, safety or cost of using epidural therapy for treating severe pre-eclampsia in non-labouring women.High-quality randomised controlled trials are needed to evaluate the use of epidural agents as therapy for treatment of severe pre-eclampsia. The rationale for the use of epidural is well-founded. However there is insufficient evidence from randomised controlled trials to show that the effect of epidural translates into improved maternal and fetal outcomes. Thus, there is a need for larger, well-designed studies to come to an evidence-based conclusion as to whether the lowering of vasomotor tone by epidural therapy results in better maternal and fetal outcomes and for how long that could be maintained. Another important question that needs to be answered is how long should extended epidural be used to ensure any potential clinical benefits and what could be the associated side effects and costs. Interactions with other modalities of treatment and women's satisfaction could represent other avenues of research.
Topics: Adrenal Cortex Hormones; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthetics, Local; Anticonvulsants; Antihypertensive Agents; Bupivacaine; Dipyridamole; Female; Humans; Plasma Substitutes; Pre-Eclampsia; Pregnancy; Vasodilator Agents
PubMed: 29181841
DOI: 10.1002/14651858.CD009540.pub2 -
The Journal of Rheumatology Sep 2017Magnetic resonance imaging (MRI) has been increasingly recognized as a critical tool for the assessment of patients with rheumatoid arthritis (RA) and is able to... (Review)
Review
OBJECTIVE
Magnetic resonance imaging (MRI) has been increasingly recognized as a critical tool for the assessment of patients with rheumatoid arthritis (RA) and is able to reliably identify synovitis, bone marrow edema, bone erosion, and joint space narrowing (JSN)/cartilage loss. Understanding the exact relationship between each MRI feature and local synovial pathobiology is critical to dissect disease pathogenesis as well as develop future predictive models.
METHODS
A systematic review was performed of the current published literature examining the relationship between MRI abnormalities and synovial pathobiology in patients with RA.
RESULTS
Eighteen studies were identified; most focused on validation of MRI as a tool to detect and quantify synovitis, with a significant relationship demonstrated. Additionally, from the limited data available, a critical role seems likely for synovial pathways, at least in driving joint damage. However, there was a lack of data examining the relationship between synovial pathobiology and bone marrow abnormalities and JSN.
CONCLUSION
Although understanding the interrelationship of these disease biomarkers offers the potential to enhance the predictive validity of modern imaging with concomitant synovial pathobiological analysis, further studies integrating MRI with synovial tissue analysis in well-controlled cohorts at distinct disease stages before and after therapeutic intervention are required to achieve this.
Topics: Arthritis, Rheumatoid; Humans; Magnetic Resonance Imaging; Synovial Membrane; Synovitis
PubMed: 28711880
DOI: 10.3899/jrheum.161314 -
Parkinsonism & Related Disorders Nov 2016Deep brain stimulation (DBS) is effective for some neurological and psychiatric conditions. Idiopathic delayed-onset edema (IDE) surrounding the leads has been... (Review)
Review
INTRODUCTION
Deep brain stimulation (DBS) is effective for some neurological and psychiatric conditions. Idiopathic delayed-onset edema (IDE) surrounding the leads has been anecdotally reported. The etiology, predisposing factors and prognosis of this complication are unknown. We present a multicenter case series of patients with IDE, and a systematic literature review, aimed at defining the pathophysiology and identifying appropriate treatment strategies.
METHODS
IDE was defined as edema along the DBS lead, occurring ≥72 h postoperatively, in absence of trauma, vascular events or infection. Information on patients with IDE was collected in a standardized way. A systematic search was performed in Pubmed.
RESULTS
Twelve new patients presenting with 14 episodes of IDE are described. From the literature, 38 patients were identified. No common surgical aspects or patient-related factors were identified as risk predictors for the onset of IDE. Symptoms included deterioration of the stimulation effect, seizures and focal neurological signs. Although the condition is self-limiting, with symptoms resolution in 28.5 days on average, three patients underwent surgical revision and seven received antibiotics.
CONCLUSIONS
IDE is a rare complication of DBS procedures, presenting from few days to months after surgery. Symptoms can be mild and not-specific, and the condition is self-limiting. The diagnosis of IDE is made after exclusion of vascular events or infections. The pathophysiology is still unexplained. The recognition of this complication can help avoiding unnecessary surgical procedures (system explantation) and antibiotic treatment.
Topics: Brain Edema; Databases, Bibliographic; Deep Brain Stimulation; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies
PubMed: 27622967
DOI: 10.1016/j.parkreldis.2016.09.007