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The Cochrane Database of Systematic... Jan 2018Tonic-clonic convulsions and convulsive status epilepticus (currently defined as a tonic-clonic convulsion lasting at least 30 minutes) are medical emergencies and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tonic-clonic convulsions and convulsive status epilepticus (currently defined as a tonic-clonic convulsion lasting at least 30 minutes) are medical emergencies and require urgent and appropriate anticonvulsant treatment. International consensus is that an anticonvulsant drug should be administered for any tonic-clonic convulsion that has been continuing for at least five minutes. Benzodiazepines (diazepam, lorazepam, midazolam) are traditionally regarded as first-line drugs and phenobarbital, phenytoin and paraldehyde as second-line drugs. This is an update of a Cochrane Review first published in 2002 and updated in 2008.
OBJECTIVES
To evaluate the effectiveness and safety of anticonvulsant drugs used to treat any acute tonic-clonic convulsion of any duration, including established convulsive (tonic-clonic) status epilepticus in children who present to a hospital or emergency medical department.
SEARCH METHODS
For the latest update we searched the Cochrane Epilepsy Group's Specialised Register (23 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 23 May 2017), MEDLINE (Ovid, 1946 to 23 May 2017), ClinicalTrials.gov (23 May 2017), and the WHO International Clinical Trials Registry Platform (ICTRP, 23 May 2017).
SELECTION CRITERIA
Randomised and quasi-randomised trials comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and extracted data. We contacted study authors for additional information.
MAIN RESULTS
The review includes 18 randomised trials involving 2199 participants, and a range of drug treatment options, doses and routes of administration (rectal, buccal, nasal, intramuscular and intravenous). The studies vary by design, setting and population, both in terms of their ages and also in their clinical situation. We have made many comparisons of drugs and of routes of administration of drugs in this review; our key findings are as follows:(1) This review provides only low- to very low-quality evidence comparing buccal midazolam with rectal diazepam for the treatment of acute tonic-clonic convulsions (risk ratio (RR) for seizure cessation 1.25, 95% confidence interval (CI) 1.13 to 1.38; 4 trials; 690 children). However, there is uncertainty about the effect and therefore insufficient evidence to support its use. There were no included studies which compare intranasal and buccal midazolam.(2) Buccal and intranasal anticonvulsants were shown to lead to similar rates of seizure cessation as intravenous anticonvulsants, e.g. intranasal lorazepam appears to be as effective as intravenous lorazepam (RR 0.96, 95% CI 0.82 to 1.13; 1 trial; 141 children; high-quality evidence) and intranasal midazolam was equivalent to intravenous diazepam (RR 0.98, 95% CI 0.91 to 1.06; 2 trials; 122 children; moderate-quality evidence).(3) Intramuscular midazolam also showed a similar rate of seizure cessation to intravenous diazepam (RR 0.97, 95% CI 0.87 to 1.09; 2 trials; 105 children; low-quality evidence).(4) For intravenous routes of administration, lorazepam appears to be as effective as diazepam in stopping acute tonic clonic convulsions: RR 1.04, 95% CI 0.94 to 1.16; 3 trials; 414 children; low-quality evidence. Furthermore, we found no statistically significant or clinically important differences between intravenous midazolam and diazepam (RR for seizure cessation 1.08, 95% CI 0.97 to 1.21; 1 trial; 80 children; moderate-quality evidence) or intravenous midazolam and lorazepam (RR for seizure cessation 0.98, 95% CI 0.91 to 1.04; 1 trial; 80 children; moderate-quality evidence). In general, intravenously-administered anticonvulsants led to more rapid seizure cessation but this was usually compromised by the time taken to establish intravenous access.(5) There is limited evidence from a single trial to suggest that intranasal lorazepam may be more effective than intramuscular paraldehyde in stopping acute tonic-clonic convulsions (RR 1.22, 95% CI 0.99 to 1.52; 160 children; moderate-quality evidence).(6) Adverse side effects were observed and reported very infrequently in the included studies. Respiratory depression was the most common and most clinically relevant side effect and, where reported, the frequency of this adverse event was observed in 0% to up to 18% of children. None of the studies individually demonstrated any difference in the rates of respiratory depression between the different anticonvulsants or their different routes of administration; but when pooled, three studies (439 children) provided moderate-quality evidence that lorazepam was significantly associated with fewer occurrences of respiratory depression than diazepam (RR 0.72, 95% CI 0.55 to 0.93).Much of the evidence provided in this review is of mostly moderate to high quality. However, the quality of the evidence provided for some important outcomes is low to very low, particularly for comparisons of non-intravenous routes of drug administration. Low- to very low-quality evidence was provided where limited data and imprecise results were available for analysis, methodological inadequacies were present in some studies which may have introduced bias into the results, study settings were not applicable to wider clinical practice, and where inconsistency was present in some pooled analyses.
AUTHORS' CONCLUSIONS
We have not identified any new high-quality evidence on the efficacy or safety of an anticonvulsant in stopping an acute tonic-clonic convulsion that would inform clinical practice. There appears to be a very low risk of adverse events, specifically respiratory depression. Intravenous lorazepam and diazepam appear to be associated with similar rates of seizure cessation and respiratory depression. Although intravenous lorazepam and intravenous diazepam lead to more rapid seizure cessation, the time taken to obtain intravenous access may undermine this effect. In the absence of intravenous access, buccal midazolam or rectal diazepam are therefore acceptable first-line anticonvulsants for the treatment of an acute tonic-clonic convulsion that has lasted at least five minutes. There is no evidence provided by this review to support the use of intranasal midazolam or lorazepam as alternatives to buccal midazolam or rectal diazepam.
Topics: Administration, Inhalation; Administration, Oral; Administration, Rectal; Anticonvulsants; Child; Diazepam; Epilepsy, Tonic-Clonic; Humans; Injections, Intramuscular; Injections, Intravenous; Lorazepam; Midazolam; Randomized Controlled Trials as Topic; Status Epilepticus
PubMed: 29320603
DOI: 10.1002/14651858.CD001905.pub3 -
The Cochrane Database of Systematic... Mar 2018Vitamin B deficiency is common, and the incidence increases with age. Most people with vitamin B deficiency are treated in primary care with intramuscular (IM) vitamin... (Review)
Review
BACKGROUND
Vitamin B deficiency is common, and the incidence increases with age. Most people with vitamin B deficiency are treated in primary care with intramuscular (IM) vitamin B. Doctors may not be prescribing oral vitamin B formulations because they may be unaware of this option or have concerns regarding its effectiveness.
OBJECTIVES
To assess the effects of oral vitamin B versus intramuscular vitamin B for vitamin B deficiency.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and LILACS, as well as the WHO ICTRP and ClinicalTrials.gov. The latest search date was 17 July 2017. We applied no language restrictions. We also contacted authors of relevant trials to enquire about other published or unpublished studies and ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing the effect of oral versus IM vitamin B for vitamin B deficiency.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were serum vitamin B levels, clinical signs and symptoms of vitamin B deficiency, and adverse events. Secondary outcomes were health-related quality of life, acceptability to patients, haemoglobin and mean corpuscular volume, total homocysteine and serum methylmalonic acid levels, and socioeconomic effects. We used GRADE to assess the quality of the evidence for important outcomes. We did not perform meta-analyses due to the small number of included trials and substantial clinical heterogeneity.
MAIN RESULTS
Three RCTs met our inclusion criteria. The trials randomised 153 participants (74 participants to oral vitamin B and 79 participants to IM vitamin B). Treatment duration and follow-up ranged between three and four months. The mean age of participants ranged from 38.6 to 72 years. The treatment frequency and daily dose of vitamin B in the oral and IM groups varied among trials. Only one trial had low or unclear risk of bias across all domains and outcome measures. Two trials reported data for serum vitamin B levels. The overall quality of evidence for this outcome was low due to serious imprecision (low number of trials and participants). In two trials employing 1000 μg/day oral vitamin B, there was no clinically relevant difference in vitamin B levels when compared with IM vitamin B. One trial used 2000 μg/day vitamin B and demonstrated a mean difference of 680 pg/mL (95% confidence interval 392.7 to 967.3) in favour of oral vitamin B. Two trials reported data on adverse events (very low-quality evidence due to risk of performance bias, detection bias, and serious imprecision). One trial stated that no treatment-related adverse events were seen in both the oral and IM vitamin B groups. One trial reported that 2 of 30 participants (6.7%) in the oral vitamin B group left the trial early due to adverse events. Orally taken vitamin B showed lower treatment-associated costs than IM vitamin B in one trial (low-quality evidence due to serious imprecision). No trial reported on clinical signs and symptoms of vitamin B deficiency, health-related quality of life, or acceptability of the treatment scheme.
AUTHORS' CONCLUSIONS
Low quality evidence shows oral and IM vitamin B having similar effects in terms of normalising serum vitamin B levels, but oral treatment costs less. We found very low-quality evidence that oral vitamin B appears as safe as IM vitamin B. Further trials should conduct better randomisation and blinding procedures, recruit more participants, and provide adequate reporting. Future trials should also measure important outcomes such as the clinical signs and symptoms of vitamin B deficiency, health related-quality of life, socioeconomic effects, and report adverse events adequately, preferably in a primary care setting.
Topics: Administration, Oral; Aged; Humans; Injections, Intramuscular; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex
PubMed: 29543316
DOI: 10.1002/14651858.CD004655.pub3 -
Journal of Patient Safety Dec 2021Delivery of intravenous medications in hospitals is a complex process posing to systemic risks for errors. The aim of this study was to identify systemic causes of...
OBJECTIVES
Delivery of intravenous medications in hospitals is a complex process posing to systemic risks for errors. The aim of this study was to identify systemic causes of in-hospital intravenous medication errors.
METHODS
A systematic review adhering to PRISMA guidelines was conducted. We searched MEDLINE (Ovid), Scopus, CINAHL, and EMB reviews for articles published between January 2005 and June 2016. Peer-reviewed journal articles published in English were included. Two reviewers independently selected articles according to a predetermined PICO tool. The quality of studies was assessed using the GRADE system and the evidence analyzed using qualitative content analysis.
RESULTS
Eleven studies from six countries were included in the analysis. We identified systemic causes related to prescribing (n = 6 studies), preparation (n = 6), administration (n = 6), dispensing and storage (n = 5), and treatment monitoring (n = 2). Administration, prescribing, and preparation were the process phases most prone to systemic errors. Insufficient actions to secure safe use of high-alert medications, lack of knowledge of the drug, calculation tasks, failure in double-checking procedures, and confusion between look-alike, sound-alike medications were the leading causes of intravenous medication errors. The number of the included studies was limited, all of them being observational studies and graded as low quality.
CONCLUSIONS
Current intravenous medication systems remain vulnerable, which can result in patient harm. Our findings suggest further focus on medication safety activities related to administration, prescribing, and preparation of intravenous medications. This study provides healthcare organizations with preliminary knowledge about systemic causes of intravenous medication errors, but more rigorous evidence is needed.
Topics: Administration, Intravenous; Hospitals; Humans; Medication Errors; Pharmaceutical Preparations
PubMed: 32011427
DOI: 10.1097/PTS.0000000000000632 -
The Cochrane Database of Systematic... Jun 2023Age-related macular degeneration (AMD) is a common eye disease and leading cause of sight loss worldwide. Despite its high prevalence and increasing incidence as... (Review)
Review
BACKGROUND
Age-related macular degeneration (AMD) is a common eye disease and leading cause of sight loss worldwide. Despite its high prevalence and increasing incidence as populations age, AMD remains incurable and there are no treatments for most patients. Mounting genetic and molecular evidence implicates complement system overactivity as a key driver of AMD development and progression. The last decade has seen the development of several novel therapeutics targeting complement in the eye for the treatment of AMD. This review update encompasses the results of the first randomised controlled trials in this field.
OBJECTIVES
To assess the effects and safety of complement inhibitors in the prevention or treatment of AMD.
SEARCH METHODS
We searched CENTRAL on the Cochrane Library, MEDLINE, Embase, LILACS, Web of Science, ISRCTN registry, ClinicalTrials.gov, and the WHO ICTRP to 29 June 2022 with no language restrictions. We also contacted companies running clinical trials for unpublished data.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with parallel groups and comparator arms that studied complement inhibition for advanced AMD prevention/treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed search results and resolved discrepancies through discussion. Outcome measures evaluated at one year included change in best-corrected visual acuity (BCVA), untransformed and square root-transformed geographic atrophy (GA) lesion size progression, development of macular neovascularisation (MNV) or exudative AMD, development of endophthalmitis, loss of ≥ 15 letters of BCVA, change in low luminance visual acuity, and change in quality of life. We assessed risk of bias and evidence certainty using Cochrane risk of bias and GRADE tools.
MAIN RESULTS
Ten RCTs with 4052 participants and eyes with GA were included. Nine evaluated intravitreal (IVT) administrations against sham, and one investigated an intravenous agent against placebo. Seven studies excluded patients with prior MNV in the non-study eye, whereas the three pegcetacoplan studies did not. The risk of bias in the included studies was low overall. We also synthesised results of two intravitreal agents (lampalizumab, pegcetacoplan) at monthly and every-other-month (EOM) dosing intervals. Efficacy and safety of IVT lampalizumab versus sham for GA For 1932 participants in three studies, lampalizumab did not meaningfully change BCVA given monthly (+1.03 letters, 95% confidence interval (CI) -0.19 to 2.25) or EOM (+0.22 letters, 95% CI -1.00 to 1.44) (high-certainty evidence). For 1920 participants, lampalizumab did not meaningfully change GA lesion growth given monthly (+0.07 mm², 95% CI -0.09 to 0.23; moderate-certainty due to imprecision) or EOM (+0.07 mm², 95% CI -0.05 to 0.19; high-certainty). For 2000 participants, lampalizumab may have also increased MNV risk given monthly (RR 1.77, 95% CI 0.73 to 4.30) and EOM (RR 1.70, 95% CI 0.67 to 4.28), based on low-certainty evidence. The incidence of endophthalmitis in patients treated with monthly and EOM lampalizumab was 4 per 1000 (0 to 87) and 3 per 1000 (0 to 62), respectively, based on moderate-certainty evidence. Efficacy and safety of IVT pegcetacoplan versus sham for GA For 242 participants in one study, pegcetacoplan probably did not meaningfully change BCVA given monthly (+1.05 letters, 95% CI -2.71 to 4.81) or EOM (-1.42 letters, 95% CI -5.25 to 2.41), as supported by moderate-certainty evidence. In contrast, for 1208 participants across three studies, pegcetacoplan meaningfully reduced GA lesion growth when given monthly (-0.38 mm², 95% CI -0.57 to -0.19) and EOM (-0.29 mm², 95% CI -0.44 to -0.13), with high certainty. These reductions correspond to 19.2% and 14.8% versus sham, respectively. A post hoc analysis showed possibly greater benefits in 446 participants with extrafoveal GA given monthly (-0.67 mm², 95% CI -0.98 to -0.36) and EOM (-0.60 mm², 95% CI -0.91 to -0.30), representing 26.1% and 23.3% reductions, respectively. However, we did not have data on subfoveal GA growth to undertake a formal subgroup analysis. In 1502 participants, there is low-certainty evidence that pegcetacoplan may have increased MNV risk when given monthly (RR 4.47, 95% CI 0.41 to 48.98) or EOM (RR 2.29, 95% CI 0.46 to 11.35). The incidence of endophthalmitis in patients treated with monthly and EOM pegcetacoplan was 6 per 1000 (1 to 53) and 8 per 1000 (1 to 70) respectively, based on moderate-certainty evidence. Efficacy and safety of IVT avacincaptad pegol versus sham for GA In a study of 260 participants with extrafoveal or juxtafoveal GA, monthly avacincaptad pegol probably did not result in a clinically meaningful change in BCVA at 2 mg (+1.39 letters, 95% CI -5.89 to 8.67) or 4 mg (-0.28 letters, 95% CI -8.74 to 8.18), based on moderate-certainty evidence. Despite this, the drug was still found to have probably reduced GA lesion growth, with estimates of 30.5% reduction at 2 mg (-0.70 mm², 95% CI -1.99 to 0.59) and 25.6% reduction at 4 mg (-0.71 mm², 95% CI -1.92 to 0.51), based on moderate-certainty evidence. Avacincaptad pegol may have also increased the risk of developing MNV (RR 3.13, 95% CI 0.93 to 10.55), although this evidence is of low certainty. There were no cases of endophthalmitis reported in this study.
AUTHORS' CONCLUSIONS
Despite confirmation of the negative findings of intravitreal lampalizumab across all endpoints, local complement inhibition with intravitreal pegcetacoplan meaningfully reduces GA lesion growth relative to sham at one year. Inhibition of complement C5 with intravitreal avacincaptad pegol is also an emerging therapy with probable benefits on anatomical endpoints in the extrafoveal or juxtafoveal GA population. However, there is currently no evidence that complement inhibition with any agent improves functional endpoints in advanced AMD; further results from the phase 3 studies of pegcetacoplan and avacincaptad pegol are eagerly awaited. Progression to MNV or exudative AMD is a possible emergent adverse event of complement inhibition, requiring careful consideration should these agents be used clinically. Intravitreal administration of complement inhibitors is probably associated with a small risk of endophthalmitis, which may be higher than that of other intravitreal therapies. Further research is likely to have an important impact on our confidence in the estimates of adverse effects and may change these. The optimal dosing regimens, treatment duration, and cost-effectiveness of such therapies are yet to be established.
Topics: Humans; Administration, Intravenous; Complement Inactivating Agents; Endophthalmitis; Geographic Atrophy; Macular Degeneration
PubMed: 37314061
DOI: 10.1002/14651858.CD009300.pub3 -
Critical Care (London, England) Mar 2023Current practice guidelines for optimal infusion rates during early intravenous hydration in patients with acute pancreatitis (AP) remain inconsistent. This systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current practice guidelines for optimal infusion rates during early intravenous hydration in patients with acute pancreatitis (AP) remain inconsistent. This systematic review and meta-analysis aimed to compare treatment outcomes between aggressive and non-aggressive intravenous hydration in severe and non-severe AP.
METHODS
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We systematically searched PubMed, Embase and Cochrane Library for randomized controlled trials (RCTs) on November 23, 2022, and hand-searched the reference lists of included RCTs, relevant review articles and clinical guidelines. We included RCTs that compared clinical outcomes from aggressive and non-aggressive intravenous hydration in AP. Meta-analysis was performed using a random-effects model for participants with severe AP and non-severe AP. Our primary outcome was all-cause mortality, and several secondary outcomes included fluid-related complications, clinical improvement and APACHE II scores within 48 h.
RESULTS
We included a total of 9 RCTs with 953 participants. The meta-analysis indicated that, compared to non-aggressive intravenous hydration, aggressive intravenous hydration significantly increased mortality risk in severe AP (pooled RR: 2.45, 95% CI: 1.37, 4.40), while the result in non-severe AP was inconclusive (pooled RR: 2.26, 95% CI: 0.54, 9.44). However, aggressive intravenous hydration significantly increased fluid-related complication risk in both severe (pooled RR: 2.22, 95% CI 1.36, 3.63) and non-severe AP (pooled RR: 3.25, 95% CI: 1.53, 6.93). The meta-analysis indicated worse APACHE II scores (pooled mean difference: 3.31, 95% CI: 1.79, 4.84) in severe AP, and no increased likelihood of clinical improvement (pooled RR:1.20, 95% CI: 0.63, 2.29) in non-severe AP. Sensitivity analyses including only RCTs with goal-directed fluid therapy after initial fluid resuscitation therapy yielded consistent results.
CONCLUSIONS
Aggressive intravenous hydration increased the mortality risk in severe AP, and fluid-related complication risk in both severe and non-severe AP. More conservative intravenous fluid resuscitation protocols for AP are suggested.
Topics: Humans; Pancreatitis; Administration, Intravenous; Treatment Outcome; Resuscitation; Fluid Therapy
PubMed: 36949459
DOI: 10.1186/s13054-023-04401-0 -
The Cochrane Database of Systematic... Apr 2015Inadvertent perioperative hypothermia (a drop in core temperature to below 36°C) occurs because of interference with normal temperature regulation by anaesthetic drugs,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inadvertent perioperative hypothermia (a drop in core temperature to below 36°C) occurs because of interference with normal temperature regulation by anaesthetic drugs, exposure of skin for prolonged periods and receipt of large volumes of intravenous and irrigation fluids. If the temperature of these fluids is below core body temperature, they can cause significant heat loss. Warming intravenous and irrigation fluids to core body temperature or above might prevent some of this heat loss and subsequent hypothermia.
OBJECTIVES
To estimate the effectiveness of preoperative or intraoperative warming, or both, of intravenous and irrigation fluids in preventing perioperative hypothermia and its complications during surgery in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE Ovid SP (1956 to 4 February 2014), EMBASE Ovid SP (1982 to 4 February 2014), the Institute for Scientific Information (ISI) Web of Science (1950 to 4 February 2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCOhost (1980 to 4 February 2014) and reference lists of identified articles. We also searched the Current Controlled Trials website and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomized controlled trials or quasi-randomized controlled trials comparing fluid warming methods versus standard care or versus other warming methods used to maintain normothermia.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from eligible trials and settled disputes with a third review author. We contacted study authors to ask for additional details when needed. We collected data on adverse events only if they were reported in the trials.
MAIN RESULTS
We included in this review 24 studies with a total of 1250 participants. The trials included various numbers and types of participants. Investigators used a range of methods to warm fluids to temperatures between 37°C and 41°C. We found that evidence was of moderate quality because descriptions of trial design were often unclear, resulting in high or unclear risk of bias due to inappropriate or unclear randomization and blinding procedures. These factors may have influenced results in some way. Our protocol specified the risk of hypothermia as the primary outcome; as no trials reported this, we decided to include data related to mean core temperature. The only secondary outcome reported in the trials that provided useable data was shivering. Evidence was unclear regarding the effects of fluid warming on bleeding. No data were reported on our other specified outcomes of cardiovascular complications, infection, pressure ulcers, bleeding, mortality, length of stay, unplanned intensive care admission and adverse events.Researchers found that warmed intravenous fluids kept the core temperature of study participants about half a degree warmer than that of participants given room temperature intravenous fluids at 30, 60, 90 and 120 minutes, and at the end of surgery. Warmed intravenous fluids also further reduced the risk of shivering compared with room temperature intravenous fluidsInvestigators reported no statistically significant differences in core body temperature or shivering between individuals given warmed and room temperature irrigation fluids.
AUTHORS' CONCLUSIONS
Warm intravenous fluids appear to keep patients warmer during surgery than room temperature fluids. It is unclear whether the actual differences in temperature are clinically meaningful, or if other benefits or harms are associated with the use of warmed fluids. It is also unclear if using fluid warming in addition to other warming methods confers any benefit, as a ceiling effect is likely when multiple methods of warming are used.
Topics: Administration, Intravenous; Anesthesia; Body Temperature; Hot Temperature; Humans; Hypothermia; Infusions, Intravenous; Randomized Controlled Trials as Topic; Shivering; Therapeutic Irrigation
PubMed: 25866139
DOI: 10.1002/14651858.CD009891.pub2 -
Journal of Crohn's & Colitis Jul 20215-Aminosalicylates [5-ASAs] are the mainstay of treatment for ulcerative colitis [UC]. The optimum preparation, dose, and route of administration for UC remain unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
5-Aminosalicylates [5-ASAs] are the mainstay of treatment for ulcerative colitis [UC]. The optimum preparation, dose, and route of administration for UC remain unclear. We conducted a network meta-analysis to examine this issue.
METHODS
We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to December 2020. We included randomised controlled trials [RCTs] comparing oral, topical, or combined oral and topical 5-ASAs, with each other or placebo for induction of remission or prevention of relapse of UC. Results were reported as pooled relative risks [RRs] with 95% confidence intervals [CIs] to summarise effect of each comparison tested, with treatments ranked according to P-score.
RESULTS
We identified 40 RCTs for induction of remission and 23 for prevention of relapse. Topical mesalazine [P-score 0.99], or oral and topical mesalazine combined [P-score 0.87] ranked first and second for clinical and endoscopic remission combined. Combined therapy ranked first in trials where ≥50% of patients had left-sided/extensive disease, and topical mesalazine first in trials where ≥50% of patients had proctitis/proctosigmoiditis. High-dose [≥3.3 g/day] oral mesalazine ranked third in most analyses, with the most trials and most patients. For relapse of disease activity, combined therapy and high-dose oral mesalazine ranked first and second, with topical mesalazine third. 5-ASAs were safe and well tolerated, regardless of regimen.
CONCLUSIONS
Our results support previous evidence; however, higher doses of oral mesalazine had more evidence for induction of remission than combined therapy and were significantly more efficacious than lower doses. Future RCTs should better establish the role of combined therapy for induction of remission, as well as optimal doses of oral 5-ASAs to prevent relapse.
Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Humans; Mesalamine; Network Meta-Analysis
PubMed: 33433562
DOI: 10.1093/ecco-jcc/jjab010 -
BMJ Clinical Evidence Aug 2011Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent.... (Review)
Review
INTRODUCTION
Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent. Bronchiectasis may cause signs of chronic obstructive pulmonary disease. It can also be associated with cystic fibrosis and other congenital disorders, foreign body inhalation, and other causes of lung damage.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (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). We performed a GRADE evaluation of the quality of evidence for interventions.
RESULTS
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergic therapy, beta(2) agonists, bronchopulmonary hygiene physical therapy, corticosteroids (inhaled, oral), exercise or physical training, hyperosmolar agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral), mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, and surgery.
Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Bronchiectasis; Cystic Fibrosis; Humans; Leukotriene Antagonists; Lung
PubMed: 21846412
DOI: No ID Found -
Frontiers in Psychiatry 2021Over the past 20 years or so, the drug misuse scenario has seen the emergence of both prescription-only and over-the-counter (OTC) medications being reported as...
Over the past 20 years or so, the drug misuse scenario has seen the emergence of both prescription-only and over-the-counter (OTC) medications being reported as ingested for recreational purposes. OTC drugs such as antihistamines, cough/cold medications, and decongestants are reportedly the most popular in being diverted and misused. While the current related knowledge is limited, the aim here was to examine the published clinical data on OTC misuse, focusing on antihistamines (e.g., diphenhydramine, promethazine, chlorpheniramine, and dimenhydrinate), dextromethorphan (DXM)- and codeine-based cough medicines, and the nasal decongestant pseudoephedrine. A systematic literature review was carried out with the help of Scopus, Web of Science databases, and the related gray literature. For data gathering purposes, both the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and PROSPERO guidelines were followed (PROSPERO identification code CRD42020209261). After completion of the selection, eligibility, and screening phases, some 92 articles were here taken into consideration; case reports, surveys, and retrospective case series analyses were included. Findings were organized according to the specific OTC recorded. Most articles focused here on DXM ( = 54) and diphenhydramine ( = 12). When specified, dosages, route(s) of administration, toxicity symptoms (including both physical and psychiatric ones), and outcomes were here reported. Results from the systematic review showed that the OTC misusing issues are both widespread worldwide and popular; vulnerable categories include adolescents and young adults, although real prevalence figures remain unknown, due to a lack of appropriate monitoring systems. Considering the potential, and at times serious, adverse effects associated with OTC misusing issues, healthcare professionals should be vigilant, and preventative actions should be designed and implemented.
PubMed: 34025478
DOI: 10.3389/fpsyt.2021.657397 -
The Cochrane Database of Systematic... Apr 2020Lumbosacral radicular pain (commonly called sciatica) is a syndrome involving patients who report radiating leg pain. Epidural corticosteroid injections deliver a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lumbosacral radicular pain (commonly called sciatica) is a syndrome involving patients who report radiating leg pain. Epidural corticosteroid injections deliver a corticosteroid dose into the epidural space, with the aim of reducing the local inflammatory process and, consequently, relieving the symptoms of lumbosacral radicular pain. This Cochrane Review is an update of a review published in Annals of Internal Medicine in 2012. Some placebo-controlled trials have been published recently, which highlights the importance of updating the previous review.
OBJECTIVES
To investigate the efficacy and safety of epidural corticosteroid injections compared with placebo injection on pain and disability in patients with lumbosacral radicular pain.
SEARCH METHODS
We searched the following databases without language limitations up to 25 September 2019: Cochrane Back and Neck group trial register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and two trial registers. We also performed citation tracking of included studies and relevant systematic reviews in the field.
SELECTION CRITERIA
We included studies that compared epidural corticosteroid injections of any corticosteroid drug to placebo injections in patients with lumbosacral radicular pain. We accepted all three anatomical approaches (caudal, interlaminar, and transforaminal) to delivering corticosteroids into the epidural space. We considered trials that included a placebo treatment as delivery of an inert substance (i.e. one with no pharmacologic activity), an innocuous substance (e.g. normal saline solution), or a pharmacologically active substance but not one considered to provide sustained benefit (e.g. local anaesthetic), either into the epidural space (i.e. to mimic epidural corticosteroid injection) or adjacent spinal tissue (i.e. subcutaneous, intramuscular, or interspinous tissue). We also included trials in which a local anaesthetic with a short duration of action was used as a placebo and injected together with corticosteroid in the intervention group.
DATA COLLECTION AND ANALYSIS
Two authors independently performed the screening, data extraction, and 'Risk of bias' assessments. In case of insufficient information, we contacted the authors of the original studies or estimated the data. We grouped the outcome data into four time points of assessment: immediate (≤ 2 weeks), short term (> 2 weeks but ≤ 3 months), intermediate term (> 3 months but < 12 months), and long term (≥ 12 months). We assessed the overall quality of evidence for each outcome and time point using the GRADE approach.
MAIN RESULTS
We included 25 clinical trials (from 29 publications) investigating the effects of epidural corticosteroid injections compared to placebo in patients with lumbosacral radicular pain. The included studies provided data for a total of 2470 participants with a mean age ranging from 37.3 to 52.8 years. Seventeen studies included participants with lumbosacral radicular pain with a diagnosis based on clinical assessment and 15 studies included participants with mixed duration of symptoms. The included studies were conducted mainly in North America and Europe. Fifteen studies did not report funding sources, five studies reported not receiving funding, and five reported receiving funding from a non-profit or government source. Eight trials reported data on pain intensity, 12 reported data on disability, and eight studies reported data on adverse events. The duration of the follow-up assessments ranged from 12 hours to 1 year. We considered eight trials to be of high quality because we judged them as having low risk of bias in four out of the five bias domains. We identified one ongoing trial in a trial registry. Epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing leg pain at short-term follow-up (mean difference (MD) -4.93, 95% confidence interval (CI) -8.77 to -1.09 on a 0 to 100 scale; 8 trials, n = 949; moderate-quality evidence (downgraded for risk of bias)). For disability, epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing disability at short-term follow-up (MD -4.18, 95% CI -6.04 to -2.17, on a 0 to 100 scale; 12 trials, n = 1367; moderate-quality evidence (downgraded for risk of bias)). The treatment effects are small, however, and may not be considered clinically important by patients and clinicians (i.e. MD lower than 10%). Most trials provided insufficient information on how or when adverse events were assessed (immediate or short-term follow-up) and only reported adverse drug reactions - that is, adverse events that the trialists attributed to the study treatment. We are very uncertain that epidural corticosteroid injections make no difference compared to placebo injection in the frequency of minor adverse events (risk ratio (RR) 1.14, 95% CI 0.91 to 1.42; 8 trials, n = 877; very low quality evidence (downgraded for risk of bias, inconsistency and imprecision)). Minor adverse events included increased pain during or after the injection, non-specific headache, post-dural puncture headache, irregular periods, accidental dural puncture, thoracic pain, non-local rash, sinusitis, vasovagal response, hypotension, nausea, and tinnitus. One study reported a major drug reaction for one patient on anticoagulant therapy who had a retroperitoneal haematoma as a complication of the corticosteroid injection.
AUTHORS' CONCLUSIONS
This study found that epidural corticosteroid injections probably slightly reduced leg pain and disability at short-term follow-up in people with lumbosacral radicular pain. In addition, no minor or major adverse events were reported at short-term follow-up after epidural corticosteroid injections or placebo injection. Although the current review identified additional clinical trials, the available evidence still provides only limited support for the use of epidural corticosteroid injections in people with lumbosacral radicular pain as the treatment effects are small, mainly evident at short-term follow-up and may not be considered clinically important by patients and clinicians (i.e. mean difference lower than 10%). According to GRADE, the quality of the evidence ranged from very low to moderate, suggesting that further studies are likely to play an important role in clarifying the efficacy and tolerability of this treatment. We recommend that further trials should attend to methodological features such as appropriate allocation concealment and blinding of care providers to minimise the potential for biased estimates of treatment and harmful effects.
Topics: Adrenal Cortex Hormones; Adult; Anesthetics, Local; Humans; Injections, Epidural; Lumbosacral Region; Middle Aged; Randomized Controlled Trials as Topic; Sciatica
PubMed: 32271952
DOI: 10.1002/14651858.CD013577