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The Cochrane Database of Systematic... Mar 2015Keratoconus is a condition of the eye that affects approximately 1 in 2000 people. The disease leads to a gradual increase in corneal curvature and decrease in visual... (Review)
Review
BACKGROUND
Keratoconus is a condition of the eye that affects approximately 1 in 2000 people. The disease leads to a gradual increase in corneal curvature and decrease in visual acuity with consequent impact on quality of life. Collagen cross-linking (CXL) with ultraviolet A (UVA) light and riboflavin (vitamin B2) is a relatively new treatment that has been reported to slow or halt the progression of the disease in its early stages.
OBJECTIVES
The objective of this review was to assess whether there is evidence that CXL is an effective and safe treatment for halting the progression of keratoconus compared to no treatment.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2014), EMBASE (January 1980 to August 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to August 2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to August 2014), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organisation International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 August 2014.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) where CXL with UVA light and riboflavin was used to treat people with keratoconus and was compared to no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. Our primary outcomes were two indicators of progression at 12 months: increase in maximum keratometry of 1.5 dioptres (D) or more and deterioration in uncorrected visual acuity of more than 0.2 logMAR.
MAIN RESULTS
We included three RCTs conducted in Australia, the United Kingdom, and the United States that enrolled a total of 225 eyes and analysed 219 eyes. The total number of people enrolled was not clear in two of the studies. Only adults were enrolled into these studies. Out of the eyes analysed, 119 had CXL (all using the epithelium-off technique) and 100 served as controls. One of these studies only reported comparative data on review outcomes. All three studies were at high risk for performance bias (lack of masking), detection bias (only one trial attempted to mask outcome assessment), and attrition bias (incomplete follow-up). It was not possible to pool data due to differences in measuring and reporting outcomes. We identified a further three unpublished trials that potentially had enrolled a total of 195 participants.There was limited evidence on the risk of progression. Analysis of the first few participants followed up to one year in one study suggested that eyes given CXL were less likely to have an increase in maximum keratometry of 1.5 D or more at 12 months compared to eyes given no treatment, but the confidence intervals (CI) were wide and compatible with no effect or more progression in the CXL group (risk ratio (RR) 0.12, 95% CI 0.01 to 2.00, 19 eyes). The same study reported the number of eyes with an increase of 2 D or more at 36 months in the whole cohort with a RR of 0.03 favouring CXL (95% CI 0.00 to 0.43, 94 eyes). Another study reported "progression" at 18 months using a different definition; people receiving CXL were less likely to progress, but again the effect was uncertain (RR 0.14, 95% CI 0.01 to 2.61, 44 eyes). We judged this to be very low-quality evidence due to the risk of bias of included studies, imprecision, indirectness and publication bias but noted that the size of the potential effect was large.On average, treated eyes had a less steep cornea (approximately 2 D less steep) (mean difference (MD) -1.92, 95% CI -2.54 to -1.30, 94 eyes, 1 RCT, very low-quality evidence) and better uncorrected visual acuity (approximately 2 lines or 10 letters better) (MD -0.20, 95% CI -0.31 to -0.09, 94 eyes, 1 RCT, very low-quality evidence) at 12 months. None of the studies reported loss of 0.2 logMAR acuity. The data on corneal thickness were inconsistent. There were no data available on quality of life or costs. Adverse effects were not uncommon but mostly transient and of low clinical significance. In one trial, 3 out of 12 participants treated with CXL had an adverse effect including corneal oedema, anterior chamber inflammation, and recurrent corneal erosions. In one trial at 3 years 3 out of 50 participants experienced adverse events including mild diffuse corneal oedema and paracentral infiltrate, peripheral corneal vascularisation, and subepithelial infiltrates and anterior chamber inflammation. No adverse effects were reported in the control groups.
AUTHORS' CONCLUSIONS
The evidence for the use of CXL in the management of keratoconus is limited due the lack of properly conducted RCTs.
Topics: Adult; Collagen; Confidence Intervals; Cross-Linking Reagents; Disease Progression; Humans; Keratoconus; Photosensitizing Agents; Randomized Controlled Trials as Topic; Riboflavin; Ultraviolet Therapy
PubMed: 25803325
DOI: 10.1002/14651858.CD010621.pub2 -
The Cochrane Database of Systematic... Apr 2014This review is an update of a review published in 2011, itself a major update of previous reviews published in 2005 and 2000, investigating the effects of gabapentin in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is an update of a review published in 2011, itself a major update of previous reviews published in 2005 and 2000, investigating the effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage chronic neuropathic pain and fibromyalgia.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain and fibromyalgia.
SEARCH METHODS
We identified randomised trials of gabapentin for chronic neuropathic pain or fibromyalgia by searching the databases MEDLINE (1966 to March 2014), EMBASE (1980 to 2014 week 10), and CENTRAL in The Cochrane Library (Issue 3 of 12, 2014). We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources, and searched Clinicaltrials.gov. Searches were run originally in 2011 and the date of the most recent search was 17 March 2014.
SELECTION CRITERIA
Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain or fibromyalgia with assessment of pain intensity, pain relief, or both, using validated scales. Participants were adults.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted efficacy and adverse event data, examined issues of study quality, and assessed risk of bias. We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.For efficacy, we calculated the number needed to treat to benefit (NNT), concentrating on at least 50% pain intensity reduction, and Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT) definitions of at least moderate and substantial benefit. For harm we calculated number needed to treat for harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model. We emphasised differences between conditions now defined as neuropathic pain, and other conditions like masticatory pain, complex regional painsyndrome type 1 (CRPS-1), and fibromyalgia.
MAIN RESULTS
Seven new studies with 1919 participants were added. Another report (147 participants) provided results for a study already included, but which previously had no usable data. A further report (170 participants) used an experimental formulation of intrathecal gabapentin. Thirty-seven studies (5633 participants) studied oral gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 84% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. There was no first tier evidence.Second tier evidence for the outcome of at least 50% pain intensity reduction, considered valuable by patients with chronic pain, showed that gabapentin was significantly better than placebo in postherpetic neuralgia (34% gabapentin versus 21% placebo; NNT 8.0, 95% CI 6.0 to 12) and painful diabetic neuropathy (38% versus 21%, NNT 5.9, 95% CI 4.6 to 8.3). There was insufficient information in other pain conditions to reach any reliable conclusion. There was no obvious difference between standard gabapentin formulations and recently-introduced extended-release or gastro-retentive formulations, or between different doses of gabapentin.Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin could expect to have at least one adverse event (62%), withdraw because of an adverse event (11%), suffer dizziness (19%), somnolence (14%), peripheral oedema (7%), and gait disturbance (9%). Serious adverse events (3%) were no more common than with placebo.There were insufficient data for direct comparisons with other active treatments, and only third tier evidence for other painful conditions.
AUTHORS' CONCLUSIONS
There was no top tier evidence that was unequivocally unbiased. Second tier evidence, with potentially important residual biases, showed that gabapentin at doses of 1200 mg or more was effective for some people with some painful neuropathic pain conditions. The outcome of at least 50% pain intensity reduction is regarded as a useful outcome of treatment by patients, and the achievement of this degree of pain relief is associated with important beneficial effects on sleep interference, fatigue, and depression, as well as quality of life, function, and work. About 35% achieved this degree of pain relief with gabapentin, compared with 21% for placebo. Over half of those treated with gabapentin will not have worthwhile pain relief. Results might vary between different neuropathic pain conditions, and the amount of evidence for gabapentin in neuropathic pain conditions except postherpetic neuralgia and painful diabetic neuropathy, and in fibromyalgia, is very limited.The levels of efficacy found for gabapentin are consistent with those found for other drug therapies in postherpetic neuralgia and painful diabetic neuropathy.
Topics: Adult; Amines; Analgesics; Chronic Disease; Chronic Pain; Cyclohexanecarboxylic Acids; Fibromyalgia; Gabapentin; Humans; Neuralgia; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid
PubMed: 24771480
DOI: 10.1002/14651858.CD007938.pub3 -
The Cochrane Database of Systematic... Apr 2014Many palliative care patients have reduced oral intake during their illness. The management of this can include the provision of medically assisted hydration with the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many palliative care patients have reduced oral intake during their illness. The management of this can include the provision of medically assisted hydration with the aim of prolonging the life of a patient, improving their quality of life, or both. This is an updated version of the original Cochrane review published in Issue 2, 2008, and updated in February 2011.
OBJECTIVES
To determine the effect of medically assisted hydration in palliative care patients on their quality and length of life.
SEARCH METHODS
We identified studies by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, CANCERLIT, Caresearch, Dissertation abstracts, SCIENCE CITATION INDEX and the reference lists of all eligible studies, key textbooks and previous systematic reviews. The date of the latest search conducted on CENTRAL, MEDLINE and EMBASE was March 2014.
SELECTION CRITERIA
All relevant randomised controlled trials (RCTs) or prospective controlled studies of medically assisted hydration in palliative care patients.
DATA COLLECTION AND ANALYSIS
We identified six relevant studies for this update. These included three RCTs (222 participants), and three prospective controlled trials (360 participants). Two review authors independently assessed the studies for quality and validity. The small number of studies and the heterogeneity of the data meant that a quantitative analysis was not possible, so we included a description of the main findings.
MAIN RESULTS
One study found that sedation and myoclonus (involuntary contractions of muscles) scores were improved more in the intervention group. Another study found that dehydration was significantly higher in the non-hydration group, but that some fluid retention symptoms (pleural effusion, peripheral oedema and ascites) were significantly higher in the hydration group. The other four studies (including the three RCTs) did not show significant differences in outcomes between the two groups. The only study that had survival as an outcome found no difference in survival between the hydration and control arms.
AUTHORS' CONCLUSIONS
Since the last version of this review, we found one new study. The studies published do not show a significant benefit in the use of medically assisted hydration in palliative care patients; however, there are insufficient good-quality studies to inform definitive recommendations for practice with regard to the use of medically assisted hydration in palliative care patients.
Topics: Adult; Controlled Clinical Trials as Topic; Dehydration; Fluid Therapy; Humans; Longevity; Myoclonus; Observational Studies as Topic; Palliative Care; Quality of Life; Terminally Ill
PubMed: 24760678
DOI: 10.1002/14651858.CD006273.pub3 -
International Journal of Clinical and... 2013To investigate the clinicopathological characteristics, prognosis, pathology, and differential diagnosis of LPM by analyzing our experience and reviewed relevant...
OBJECTIVE
To investigate the clinicopathological characteristics, prognosis, pathology, and differential diagnosis of LPM by analyzing our experience and reviewed relevant literature. We also postulated the necessity of postoperative adjuvant therapy.
METHODS
19 patients with LPM underwent surgical treatment from 2007 through 2010 in our department. The clinical charts of the patients, including surgical, histological, and follow-up records, as well as imaging studies, were analyzed retrospectively. Other 43 cases searched from the literature were also included, so that 62 LPM cases were summarized and reviewed together.
RESULTS
The summarized 62 patients comprised 30 males and 31 females aged 9 years to 79 years (40.7±18.3 years). The most common locations were convexity, skull base, para-sagittal and cervical canal. Multiple or diffuse lesions were found in 8 cases. There were 13 patients had peripheral blood abnormalities (21%). One-third of the cases had moderate to severe peritumoral brain edema. Thirty-eight patients had total resection, 12 patients not specified while 12 received subtotal resection or only biopsy. MIB-1 was available in 24 cases and a third of them were higher than 3%. Follow-up more than 3 year was only completed in 19/62 cases. Seven cases suffered recurrence and two of them died after 2 years of operation.
CONCLUSION
LPM is a very rare benign variant of intracranial meningioma. Both lesions and hematological abnormalities have a predilection for younger individuals. Preoperative diagnosis of this subtype of meningioma is still difficult. Surgical resection is the primary treatment option, and supportive care for those not totally removed is very important, because the recurrence rate for this subtype is rather low. However, the massive infiltration of lymphocytes and plasma cells in LPMs are still controversial and the long-term follow-ups are needed. Radiotherapy is not recommended, and hormonal or immune-inhibitor therapy might be helpful.
PubMed: 23936588
DOI: No ID Found -
PloS One 2012Outbreaks of Hand Foot and Mouth Disease (HFMD) have occurred in many parts of the world especially in China. We aimed to summarize the characteristics of the levels of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Outbreaks of Hand Foot and Mouth Disease (HFMD) have occurred in many parts of the world especially in China. We aimed to summarize the characteristics of the levels of blood glucose and white blood cell (WBC) counts in cases of HFMD in Mainland China and Taiwan, using meta-analysis based on systematic review of published articles.
METHODS
We systematically reviewed published studies, from the MEDLINE and WANFANG Data, about the levels of blood glucose and WBC counts in cases of HFMD until 15(th) June 2011, and quantitatively summarized the characteristics of them using meta-analysis.
RESULTS
In total, 37 studies were included in this review. In Mainland China and Taiwan, generally, the average level of blood glucose, the prevalence of hyperglycemia, WBC counts and the prevalence of leukocytosis increased with the severity of the illness. There was no significant difference in the prevalence of leukocytosis between ANS (autonomic nervous system dysregulation)/PE (pulmonary edema) group and CNS (central nervous system) group, and in the average level of blood glucose between healthy controls and mild cases of HFMD. WBC counts in cases infected by EV71 were less than those in cases infected by CA16.
CONCLUSIONS
our analyses indicated that blood glucose and WBC counts increased with the severity of HFMD disease, which would help doctors to manage patients efficiently.
Topics: Blood Glucose; China; Female; Hand, Foot and Mouth Disease; Humans; Leukocyte Count; Male; Regression Analysis
PubMed: 22235257
DOI: 10.1371/journal.pone.0029003 -
BMJ Clinical Evidence May 2011Diabetic retinopathy is the most common cause of blindness in the UK, with older people and those with worse diabetes control, hypertension, and hyperlipidaemia being... (Review)
Review
INTRODUCTION
Diabetic retinopathy is the most common cause of blindness in the UK, with older people and those with worse diabetes control, hypertension, and hyperlipidaemia being most at risk. Diabetic retinopathy can cause microaneurysms, haemorrhages, exudates, changes to blood vessels, and retinal thickening.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with diabetic retinopathy? What are the effects of treatments for vitreous haemorrhage? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 58 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: peripheral retinal laser photocoagulation, focal and grid laser photocoagulation for maculopathy, corticosteroids for macular oedema, vascular endothelial growth factor inhibitors, and vitrectomy for vitreous haemorrhage.
Topics: Diabetic Retinopathy; Humans; Injections; Macular Edema; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 21609511
DOI: No ID Found -
The Cochrane Database of Systematic... Mar 2011This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning.
OBJECTIVES
To evaluate the analgesic effectiveness and adverse effects of gabapentin for chronic neuropathic pain management.
SEARCH STRATEGY
We identified randomised trials of gabapentin in acute, chronic or cancer pain from MEDLINE, EMBASE, and CENTRAL. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources. The date of the most recent search was January 2011.
SELECTION CRITERIA
Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain with assessment of pain intensity and/or pain relief, using validated scales. Participants were adults aged 18 and over.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. We calculated numbers needed to treat to benefit (NNTs), concentrating on IMMPACT (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials) definitions of at least moderate and substantial benefit, and to harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model.
MAIN RESULTS
Twenty-nine studies (3571 participants), studied gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 78% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. Using the IMMPACT definition of at least moderate benefit, gabapentin was superior to placebo in 14 studies with 2831 participants, 43% improving with gabapentin and 26% with placebo; the NNT was 5.8 (4.8 to 7.2). Using the IMMPACT definition of substantial benefit, gabapentin was superior to placebo in 13 studies with 2627 participants, 31% improving with gabapentin and 17% with placebo; the NNT was 6.8 (5.6 to 8.7). These estimates of efficacy are more conservative than those reported in a previous review. Data from few studies and participants were available for other painful conditions.Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin can expect to have at least one adverse event (66%), withdraw because of an adverse event (12%), suffer dizziness (21%), somnolence (16%), peripheral oedema (8%), and gait disturbance (9%). Serious adverse events (4%) were no more common than with placebo.There were insufficient data for comparisons with other active treatments.
AUTHORS' CONCLUSIONS
Gabapentin provides pain relief of a high level in about a third of people who take if for painful neuropathic pain. Adverse events are frequent, but mostly tolerable. More conservative estimates of efficacy resulted from using better definitions of efficacy outcome at higher, clinically important, levels, combined with a considerable increase in the numbers of studies and participants available for analysis.
Topics: Amines; Analgesics; Chronic Disease; Cyclohexanecarboxylic Acids; Fibromyalgia; Gabapentin; Humans; Neuralgia; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid
PubMed: 21412914
DOI: 10.1002/14651858.CD007938.pub2 -
Epilepsia Apr 2011Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta-analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose-response relationship.
METHODS
We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo-controlled, double-blind RCTs investigating the therapeutic effects of pregabalin in adults with any condition. Studies had to include at least 20 subjects per arm and have a duration of at least 4 weeks. AEs were assessed for their association with pregabalin after identification/exclusion of synonyms, rare AEs, and nonassessable AEs due to methodologic limitations. We used relative risks (RRs) to assess the association of any [99% confidence intervals (CIs)] or serious AEs (95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate dose-response relationships of pregabalin AEs.
KEY FINDINGS
Thirty-eight RCTs were included in our study. Of 39 AEs, 20 (51%) were significantly associated with pregabalin (dizziness, vertigo, incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia, tremor, somnolence, confusional state, disturbance in attention, thinking abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth, constipation). The highest RRs were found for cognition/coordination AEs. There was no significant association between serious AEs and pregabalin. There was a selective dose-response pattern in the onset of pregabalin AEs, with certain AEs appearing at lower doses than others.
SIGNIFICANCE
Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose-response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta-analyses of AED tolerability profiles RCTs performed in different conditions.
Topics: Analgesics; Anticonvulsants; Epilepsy; Humans; Neuralgia; Outcome Assessment, Health Care; Pregabalin; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid
PubMed: 21320112
DOI: 10.1111/j.1528-1167.2010.02966.x -
Respiratory Research Jan 2010Previous meta-analyses of treatments for pulmonary arterial hypertension (PAH) have not shown mortality benefit from any individual class of medication. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previous meta-analyses of treatments for pulmonary arterial hypertension (PAH) have not shown mortality benefit from any individual class of medication.
METHODS
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through November 2009 for randomized trials that evaluated any pharmacotherapy in the treatment of PAH. Reference lists from included articles and recent review articles were also searched. Analysis included randomized placebo controlled trials of at least eight weeks duration and studies comparing intravenous medication to an unblinded control group.
RESULTS
1541 unique studies were identified and twenty-four articles with 3758 patients were included in the meta-analysis. Studies were reviewed and data extracted regarding study characteristics and outcomes. Data was pooled for three classes of medication: prostanoids, endothelin-receptor antagonists (ERAs), and phosphodiesterase type 5 (PDE5) inhibitors. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for mortality, 6-minute walk distance, dyspnea scores, hemodynamic parameters, and adverse effects. Mortality in the control arms was a combined 4.2% over the mean study length of 14.9 weeks. There was significant mortality benefit with prostanoid treatment (RR 0.49, CI 0.29 to 0.82), particularly comparing intravenous agents to control (RR 0.30, CI 0.14 to 0.63). Mortality benefit was not observed for ERAs (RR 0.58, CI 0.21 to 1.60) or PDE5 inhibitors (RR 0.30, CI 0.08 to 1.08). All three classes of medication improved other clinical and hemodynamic endpoints. Adverse effects that were increased in treatment arms include jaw pain, diarrhea, peripheral edema, headache, and nausea in prostanoids; and visual disturbance, dyspepsia, flushing, headache, and limb pain in PDE5 inhibitors. No adverse events were significantly associated with ERA treatment.
CONCLUSIONS
Treatment of PAH with prostanoids reduces mortality and improves multiple other clinical and hemodynamic outcomes. ERAs and PDE5 inhibitors improve clinical and hemodynamic outcomes, but have no proven effect on mortality. The long-term effects of all PAH treatment requires further study.
Topics: Antihypertensive Agents; Endothelin Receptor Antagonists; Humans; Hypertension, Pulmonary; Phosphodiesterase 5 Inhibitors; Prevalence; Prostaglandins; Randomized Controlled Trials as Topic; Registries; Survival Analysis; Survival Rate; Treatment Outcome
PubMed: 20113497
DOI: 10.1186/1465-9921-11-12 -
Rheumatology (Oxford, England) Dec 2009CNS or peripheral nervous system dysfunction sometimes occurs in Henoch-Schönlein patients. (Review)
Review
OBJECTIVE
CNS or peripheral nervous system dysfunction sometimes occurs in Henoch-Schönlein patients.
METHODS
We review all Henoch-Schönlein cases published after 1969 with CNS dysfunction without severe hypertension and neuroimaging studies (n = 35), cranial or peripheral neuropathy (n = 15), both CNS and peripheral nervous system dysfunction without severe hypertension (n = 2) or nervous system dysfunction with severe hypertension (n = 2). Forty-four of the 54 patients were <20 years of age.
RESULTS
In patients with CNS dysfunction without or with severe hypertension the following presentations were observed in decreasing order of frequency: altered level of consciousness, convulsions, focal neurological deficits, visual abnormalities and verbal disability. Imaging studies disclosed the following lesions: vascular lesions almost always involving two or more vessels, intracerebral haemorrhage, posterior subcortical oedema, diffuse brain oedema and thrombosis of the superior sagittal sinus. Following lesions were noted in the subjects with cranial or peripheral neuropathy without severe hypertension: peroneal neuropathy, peripheral facial palsy, Guillain-Barré syndrome, brachial plexopathy, posterior tibial nerve neuropathy, femoral neuropathy, ulnar neuropathy and mononeuritis multiplex. Persisting signs of either CNS (n = 9) or peripheral (n = 1) nervous system dysfunction were sometimes reported.
CONCLUSIONS
In Henoch-Schönlein syndrome, signs of nervous system dysfunction are uncommon but clinically relevant. This review helps clinicians managing Henoch-Schönlein syndrome with nervous system dysfunction.
Topics: Adolescent; Adult; Age Distribution; Central Nervous System Diseases; Child; Child, Preschool; Female; Humans; Hypertension; IgA Vasculitis; Infant; Infant, Newborn; Kidney Diseases; Male; Nervous System Diseases; Peripheral Nervous System Diseases; Young Adult
PubMed: 19797041
DOI: 10.1093/rheumatology/kep282