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JAMA Neurology Mar 2021Spontaneous intracranial hypotension (SIH) is a highly disabling but often misdiagnosed disorder. The best management options for patients with SIH are still uncertain. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Spontaneous intracranial hypotension (SIH) is a highly disabling but often misdiagnosed disorder. The best management options for patients with SIH are still uncertain.
OBJECTIVE
To provide an objective summary of the available evidence on the clinical presentation, investigations findings, and treatment outcomes for SIH.
DATA SOURCES
Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline-compliant systematic review and meta-analysis of the literature on SIH. Three databases were searched from inception to April 30, 2020: PubMed/MEDLINE, Embase, and Cochrane. The following search terms were used in each database: spontaneous intracranial hypotension, low CSF syndrome, low CSF pressure syndrome, low CSF volume syndrome, intracranial hypotension, low CSF pressure, low CSF volume, CSF hypovolemia, CSF hypovolaemia, spontaneous spinal CSF leak, spinal CSF leak, and CSF leak syndrome.
STUDY SELECTION
Original studies in English language reporting 10 or more patients with SIH were selected by consensus.
DATA EXTRACTION AND SYNTHESIS
Data on clinical presentation, investigations findings, and treatment outcomes were collected and summarized by multiple observers. Random-effect meta-analyses were used to calculate pooled estimates of means and proportions.
MAIN OUTCOMES AND MEASURES
The predetermined main outcomes were the pooled estimate proportions of symptoms of SIH, imaging findings (brain and spinal imaging), and treatment outcomes (conservative, epidural blood patches, and surgical).
RESULTS
Of 6878 articles, 144 met the selection criteria and reported on average 53 patients with SIH each (range, 10-568 patients). The most common symptoms were orthostatic headache (92% [95% CI, 87%-96%]), nausea (54% [95% CI, 46%-62%]), and neck pain/stiffness (43% [95% CI, 32%-53%]). Brain magnetic resonance imaging was the most sensitive investigation, with diffuse pachymeningeal enhancement identified in 73% (95% CI, 67%-80%) of patients. Brain magnetic resonance imaging findings were normal in 19% (95% CI, 13%-24%) of patients. Spinal neuroimaging identified extradural cerebrospinal fluid in 48% to 76% of patients. Digital subtraction myelography and magnetic resonance myelography with intrathecal gadolinium had high sensitivity in identifying the exact leak site. Lumbar puncture opening pressures were low, normal (60-200 mm H2O), and high in 67% (95% CI, 54%-80%), 32% (95% CI, 20%-44%), and 3% (95% CI, 1%-6%), respectively. Conservative treatment was effective in 28% (95% CI, 18%-37%) of patients and a single epidural blood patch was successful in 64% (95% CI, 56%-72%). Large epidural blood patches (>20 mL) had better success rates than small epidural blood patches (77% [95% CI, 63%-91%] and 66% [95% CI, 55%-77%], respectively).
CONCLUSIONS AND RELEVANCE
Spontaneous intracranial hypotension should not be excluded on the basis of a nonorthostatic headache, normal neuroimaging findings, or normal lumbar puncture opening pressure. Despite the heterogeneous nature of the studies available in the literature and the lack of controlled interventional studies, this systematic review offers a comprehensive and objective summary of the evidence on SIH that could be useful in guiding clinical practice and future research.
Topics: Blood Patch, Epidural; Conservative Treatment; Humans; Intracranial Hypotension; Magnetic Resonance Imaging; Treatment Outcome
PubMed: 33393980
DOI: 10.1001/jamaneurol.2020.4799 -
Medicina (Kaunas, Lithuania) Jun 2020Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms...
BACKGROUND AND OBJECTIVE
Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms available, which are gaining popularity for both recreational and therapeutic use. From a therapeutic perspective, oral cannabis containing Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is a promising route of administration but there is still little information about its pharmacokinetics (PK) effects in humans. The purpose of this systematic review is to provide a general overview of the available PK data on cannabis and THC after oral administration.
METHODS
A search of the published literature was conducted using the PubMed database to collect available articles describing the PK data of THC after oral administration in humans.
RESULTS
The literature search yielded 363 results, 26 of which met our inclusion criteria. The PK of oral THC has been studied using capsules (including oil content), tablets, baked goods (brownies and cookies), and oil and tea (decoctions). Capsules and tablets, which mainly correspond to pharmaceutical forms, were found to be the oral formulations most commonly studied. Overall, the results reflect the high variability in the THC absorption of oral formulations, with delayed peak plasma concentrations compared to other routes of administration.
CONCLUSIONS
Oral THC has a highly variable PK profile that differs between formulations, with seemingly higher variability in baked goods and oil forms. Overall, there is limited information available in this field. Therefore, further investigations are required to unravel the unpredictability of oral THC administration to increase the effectiveness and safety of oral formulations in medicinal use.
Topics: Administration, Oral; Dronabinol; Drug Compounding; Humans; Nitrogen Mustard Compounds
PubMed: 32585912
DOI: 10.3390/medicina56060309 -
Phytomedicine : International Journal... Dec 2019Anxiety is one of the uprising psychiatric disorders of the last decades and lavender administration has been traditionally suggested as a possible treatment. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anxiety is one of the uprising psychiatric disorders of the last decades and lavender administration has been traditionally suggested as a possible treatment. The objective of this review is to assess the efficacy of lavender, in any form and way of administration, on anxiety and anxiety-related conditions.
METHODS
The PRISMA guidelines were followed. Retrieved data were qualitatively and quantitatively synthesized. Randomized Controlled Trials (RCTs) and Non-Randomized Studies (NRSs) which investigated the efficacy of lavender, in any form and way of administration, on patients with anxiety, involved in anxiety-inducing settings or undergoing anxiety-inducing activities, compared to any type of control, without language restrictions, were identified through electronic database searches. Medline via PubMed, Scopus, Web of Science, Cochrane Library, EMBASE, and Google Scholar were systematically searched. All databases were screened up to November 2018. Risk of bias was assessed with the Cochrane risk-of-bias tool and the following domains were considered: randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases.
RESULTS
65 RCTs (7993 participants) and 25 NRSs (1200 participants) were included in the qualitative synthesis and 37 RCTs (3964 participants) were included in the quantitative synthesis. Overall, the qualitative synthesis indicated that 54 RCTs and 17 NRSs reported at least a significant result in favor of lavender use for anxiety. The quantitative synthesis showed that lavender inhalation can significantly reduce anxiety levels measured with any validated scale (Hedges' g = -0.73 [95% CI -1.00 to -0.46], p < 0.00001, 1682 participants), as well as state anxiety (Spielberger's state-trait anxiety inventory (STAI)-State mean difference = -5.99 [95% CI -9.39 to -2.59], p < 0.001, 901 participants) and trait anxiety (STAI-Trait mean difference = -8.14 [95% CI -14.44 to -1.84], p < 0.05, 196 participants). Lavender inhalation did not show a significant effect in reducing systolic blood pressure as a physiological parameter of anxiety. A significant effect in diminishing anxiety levels was also found in favor of the use of oral Silexan® 80 mg/die for at least 6 weeks (Hamilton Anxiety Scale mean difference = -2.90 [95% CI -4.86 to -0.95], p = 0.004, 1173 participants; Zung Self-rating Anxiety Scale mean difference = -2.62 [95% CI -4.84 to -0.39], p < 0.05, 451 participants) or of the administration of massage with lavender oil (Hedges' g = -0.66 [95% CI -0.97 to -0.35], p < 0.0001, 448 participants).
DISCUSSION
The most important limitation of this review is the low average quality of available studies on the topic. The majority of included RCTs were characterized by a high overall risk of bias. Another limitation regards the heterogeneity of study designs, especially with regard to non-oral ways of administration. Overall, oral administration of lavender essential oil proves to be effective in the treatment of anxiety, whereas for inhalation there is only an indication of an effect of reasonable size, due to the heterogeneity of available studies. Lavender essential oil administered through massage appears effective, but available studies are not sufficient to determine whether the benefit is due to a specific effect of lavender. Further high-quality RCTs with more homogeneous study designs are needed to confirm these findings. Available information outlines a safe profile for lavender-based interventions, although more attention should be paid to the collection and reporting of safety data in future studies. Considering these findings, since treatments with lavender essential oil generally seem safe, and, in the case of inhalation, also simple and inexpensive, they are a therapeutic option which may be considered in some clinical contexts.
OTHER
The present systematic review was not funded and was registered in PROSPERO under the following number: CRD42019130126.
Topics: Administration, Inhalation; Administration, Oral; Anxiety; Anxiety Disorders; Blood Pressure; Humans; Lavandula; Oils, Volatile; Plant Oils; Randomized Controlled Trials as Topic
PubMed: 31655395
DOI: 10.1016/j.phymed.2019.153099 -
Archives of Gynecology and Obstetrics Jun 2023To summarize available evidence comparing the transdermal and the oral administration routes of hormone replacement therapy (HRT) in postmenopausal women. (Review)
Review
PURPOSE
To summarize available evidence comparing the transdermal and the oral administration routes of hormone replacement therapy (HRT) in postmenopausal women.
METHODS
We performed a systematic review of the literature on multiple databases between January 1990 and December 2021. We included randomized controlled trials and observational studies comparing the transdermal and oral administration routes of estrogens for HRT in postmenopausal women regarding at least one of the outcomes of interest: cardiovascular risk, venous thromboembolism (VTE), lipid metabolism, carbohydrate metabolism, bone mineral density (BMD), and risk of pre-malignant and malignant endometrial lesions, or breast cancer.
RESULTS
The systematic literature search identified a total of 1369 manuscripts, of which 51 were included. Most studies were observational and of good quality, whereas the majority of randomized controlled trials presented a high or medium risk of bias. Oral and transdermal administration routes are similar regarding BMD, glucose metabolism, and lipid profile improvements, as well as do not appear different regarding breast cancer, endometrial disease, and cardiovascular risk. Identified literature provides clear evidence only for the VTE risk, which is higher with the oral administration route.
CONCLUSIONS
Available evidence comparing the transdermal and oral administration routes for HRT is limited and of low quality, recommending further investigations. VTE risk can be considered the clearest and strongest clinical difference between the two administration routes, supporting the transdermal HRT as safer than the oral administration route.
Topics: Female; Humans; Postmenopause; Estrogen Replacement Therapy; Venous Thromboembolism; Administration, Cutaneous; Estrogens; Hormone Replacement Therapy; Breast Neoplasms; Administration, Oral; Lipids
PubMed: 35713694
DOI: 10.1007/s00404-022-06647-5 -
World Journal of Emergency Surgery :... Mar 2023During medical emergencies, intraosseous (IO) access and intravenous (IV) access are methods of administering therapies and medications to patients. Treating patients in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
During medical emergencies, intraosseous (IO) access and intravenous (IV) access are methods of administering therapies and medications to patients. Treating patients in emergency medical situations is a highly time sensitive practice; however, research into the optimal access method is limited and existing systematic reviews have only considered out-of-hospital cardiac arrest (OHCA) patients. We focused on severe trauma patients and conducted a systematic review to evaluate the efficacy and efficiency of intraosseous (IO) access compared to intravenous (IV) access for trauma resuscitation in prehospital care.
MATERIALS AND METHOD
PubMed, Web of Science, Cochrane Library, EMBASE, ScienceDirect, banque de données en santé publique and CNKI databases were searched for articles published between January 1, 2000, and January 31, 2023. Adult trauma patients were included, regardless of race, nationality, and region. OHCA patients and other types of patients were excluded. The experimental and control groups received IO and IV access, respectively, in the pre-hospital and emergency departments for salvage. The primary outcome was success rate on first attempt, which was defined as secure needle position in the marrow cavity or a peripheral vein, with normal fluid flow. Secondary outcomes included mean time to resuscitation, mean procedure time, and complications.
RESULTS
Three reviewers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies; meta-analyses were then performed using Review Manager (Version 5.4; Cochrane, Oxford, UK). The success rate on first attempt was significant higher for IO access than for IV access (RR = 1.46, 95% CI [1.16, 1.85], P = 0.001). The mean procedure time was significantly reduced (MD = - 5.67, 95% CI [- 9.26, - 2.07], P = 0.002). There was no significant difference in mean time to resuscitation (MD = - 1.00, 95% CI [- 3.18, 1.17], P = 0.37) and complications (RR = 1.22, 95% CI [0.14, 10.62], P = 0.86) between the IO and IV groups.
CONCLUSION
The success rate on first attempt of IO access was much higher than that of IV access for trauma patients, and the mean procedure time of IO access was significantly less when compared to IV access. Therefore, IO access should be suggested as an urgent vascular access for hypotensive trauma patients, especially those who are under severe shock.
Topics: Adult; Humans; Emergency Medical Services; Emergency Service, Hospital; Resuscitation; Infusions, Intraosseous
PubMed: 36918947
DOI: 10.1186/s13017-023-00487-7 -
The Cochrane Database of Systematic... Oct 2016Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta. This is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density, reducing fractures and improving clinical function in people with osteogenesis imperfecta.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We additionally searched PubMed and major conference proceedings.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Register: 28 April 2016.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of osteogenesis imperfecta.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias of the included trials.
MAIN RESULTS
Fourteen trials (819 participants) were included. Overall, the trials were mainly at a low risk of bias, although selective reporting was an issue in several of the trials. Data for oral bisphosphonates versus placebo could not be aggregated; a statistically significant difference favouring oral bisphosphonates in fracture risk reduction and number of fractures was noted in two trials. No differences were reported in the remaining three trials which commented on fracture incidence. Five trials reported data for spine bone mineral density; all found statistically significant increased lumbar spine density z scores for at least one time point studied. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no statistically significant difference for the number of participants with at least one fracture, risk ratio 0.56 (95% confidence interval 0.30 to 1.06). In the remaining trial no statistically significant difference was noted in fracture incidence. For spine bone mineral density, no statistically significant difference was noted in the aggregated data from two trials, mean difference 9.96 (95% confidence interval -2.51 to 22.43). In the remaining trial a statistically significant difference in mean per cent change in spine bone mineral density z score favoured intravenous bisphosphonates at six and 12 months. Data describing growth, bone pain, and functional outcomes after oral or intravenous bisphosphonate therapy, or both, as compared to placebo were incomplete among all studies, but do not show consistent improvements in these outcomes. Two studies compared different doses of bisphosphonates. No differences were found between doses when bone mineral density, fractures, and height or length z score were assessed. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Two studies compared the intravenous bisphosphonates zoledronic acid and pamidronate. There were no significant differences in primary outcome. However, the studies were at odds as to the relative benefit of zoledronic acid over pamidronate for lumbosacral bone mineral density at 12 months.
AUTHORS' CONCLUSIONS
Bisphophonates are commonly prescribed to individuals with osteogenesis imperfecta. Current evidence, albeit limited, demonstrates oral or intravenous bisphosphonates increase bone mineral density in children and adults with this condition. These were not shown to be different in their ability to increase bone mineral density. It is unclear whether oral or intravenous bisphosphonate treatment consistently decreases fractures, though multiple studies report this independently and no studies report an increased fracture rate with treatment. The studies included here do not show bisphosphonates conclusively improve clinical status (reduce pain; improve growth and functional mobility) in people with osteogenesis imperfecta. Given their current widespread and expected continued use, the optimal method, duration of therapy and long-term safety of bisphosphonate therapy require further investigation. In addition, attention should be given to long-term fracture reduction and improvement in quality of life indicators.
Topics: Administration, Oral; Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Injections, Intravenous; Osteogenesis Imperfecta; Randomized Controlled Trials as Topic
PubMed: 27760454
DOI: 10.1002/14651858.CD005088.pub4 -
Anaesthesia Feb 2018Loop diuretics remain a fundamental pharmacological therapy to remove excess fluid and improve symptom control in acute decompensated heart failure. Several recent... (Comparative Study)
Comparative Study Meta-Analysis
Continuous infusion vs. intermittent bolus injection of furosemide in acute decompensated heart failure: systematic review and meta-analysis of randomised controlled trials.
Loop diuretics remain a fundamental pharmacological therapy to remove excess fluid and improve symptom control in acute decompensated heart failure. Several recent randomised controlled trials have examined the clinical benefit of continuous vs. bolus furosemide in acute decompensated heart failure, but have reported conflicting findings. The aim of this review was to compare the effects of continuous and bolus furosemide with regard to mortality, length of hospital stay and its efficacy profile in acute decompensated heart failure. All parallel-arm randomised controlled trials from MEDLINE, EMBASE, PubMed and the Cochrane Database of Systematic Reviews from inception until May 2017 were included. Cross-over randomised controlled trials, observational studies, case reports, case series and non-systematic reviews that involved children were excluded. Eight trials (n = 669) were eligible for inclusion. There was no difference between furosemide continuous infusion and bolus administration for all-cause mortality (four studies; n = 491; I = 0%; OR 1.65; 95%CI 0.93-2.91; p = 0.08) or duration of hospitalisation (six studies; n = 576; I = 71%; mean difference 0.27; 95%CI -1.35 to 1.89 days; p = 0.74). Continuous infusion of intravenous furosemide was associated with increased weight reduction (five studies; n = 516; I = 0%; mean difference 0.70; 95%CI 0.12-1.28 kg; p = 0.02); increased total urine output in 24 h (four studies; n = 390; I = 33%; mean difference 461.5; 95%CI 133.7-789.4 ml; p < 0.01); and reduced brain natriuretic peptide (two studies; n = 390; I = 0%; mean difference 399.5; 95%CI 152.7-646.3 ng.l ; p < 0.01), compared with the bolus group. There was no difference in the incidence of raised creatinine and hypokalaemia between the two groups. In summary, there was no difference between continuous infusion and bolus of furosemide for all-cause mortality, length of hospital stay and electrolyte disturbance, but continuous infusion was superior to bolus administration with regard to diuretic effect and reduction in brain natriuretic peptide.
Topics: Acute Disease; Diuretics; Furosemide; Heart Failure; Humans; Infusions, Intravenous; Injections, Intravenous; Length of Stay
PubMed: 28940440
DOI: 10.1111/anae.14038 -
PloS One 2020To synthesize the current evidence for subcutaneous hydration and medication infusions from systematic reviews and to assess their methodological quality.
OBJECTIVE
To synthesize the current evidence for subcutaneous hydration and medication infusions from systematic reviews and to assess their methodological quality.
INTRODUCTION
Peripheral intravascular cannula/catheter insertion is a common invasive procedure for administering fluids and medications. Venous depletion is a growing concern for several patient populations. Subcutaneous access for the administration of isotonic solutions and medications is an alternative; however, vascular access assessment and planning guidelines rarely consider this route.
METHODS
Systematic review of systematic reviews (PROSPERO CRD42018046504). We searched 6 databases published in English language from 1990 to June 2020, identifying subcutaneous infusions an alternate route for fluids or medication. Methodological quality was evaluated using AMSTAR 2 criteria and data for mechanisms of infusion and outcomes related to effectiveness, safety, efficiency and acceptability extracted. The Johanna Briggs Institute's grades of recommendation informed the strength of recommendation.
RESULTS
The search yielded 1042 potential systematic reviews; 922 were excluded through abstract and duplicate screen. Of the remaining articles, 94 were excluded, and 26 were included. Overall, evidence is strong for recommending subcutaneous hydration infusions for older adults, weak for pediatric patients and inconclusive for palliative patients. There is strong evidence for 10 medications; weak evidence supporting 28 medications; however, there are eight medications with inconclusive evidence to make a recommendation and four medications not appropriate for subcutaneous delivery.
CONCLUSION
Subcutaneous access should be considered alongside intravenous therapy for hydration in older adults, and several medications. There are additional benefits in terms of ease of use and cost-effectiveness of this mode. Inclusion of subcutaneous access in clinical guidelines may promote uptake of this route to help preserve vessel health of vulnerable patients. Further high-quality research is needed to inform subcutaneous infusion therapy in a variety of populations (including pediatrics and palliative care) and medications and clarifying the mechanism of delivery.
Topics: Dehydration; Fluid Therapy; Humans; Hypodermoclysis; Infusions, Subcutaneous
PubMed: 32833979
DOI: 10.1371/journal.pone.0237572 -
The Journal of Clinical Endocrinology... Feb 2022Injections with intramuscular (IM) testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also...
CONTEXT
Injections with intramuscular (IM) testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also the most inexpensive modality. However, they are difficult to self-administer and associated with some discomfort. Recently, subcutaneous (SC) administration of testosterone esters has gained popularity, as self-administration is easier with this route. Available data, though limited, support the feasibility of this route. Here we review the pharmacokinetics and safety of SC testosterone therapy with both long- and ultralong-acting testosterone esters. In addition, we provide guidance for clinicians on how to counsel and manage their patients who opt for the SC route.
EVIDENCE ACQUISITION
Systematic review of available literature on SC testosterone administration including clinical trials, case series, and case reports. We also review the pharmacology of testosterone absorption after SC administration.
EVIDENCE SYNTHESIS
Available evidence, though limited, suggests that SC testosterone therapy in doses similar to those given via IM route results in comparable pharmacokinetics and mean serum testosterone levels. With appropriate training, patients should be able to safely self-administer testosterone esters SC with relative ease and less discomfort compared with the IM route.
CONCLUSION
Although studies directly comparing the safety of SC vs IM administration of testosterone esters are desirable, clinicians should consider discussing the SC route with their patients because it is easier to self-administer and has the potential to improve patient adherence.
Topics: Feasibility Studies; Female; Humans; Hypogonadism; Injections, Intramuscular; Injections, Subcutaneous; Male; Self Administration; Sex Reassignment Procedures; Testosterone; Transgender Persons
PubMed: 34698352
DOI: 10.1210/clinem/dgab772 -
The Cochrane Database of Systematic... Jul 2017Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their... (Review)
Review
BACKGROUND
Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine-like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly-used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol.
OBJECTIVES
To provide an overview of the analgesic efficacy of opioids in cancer pain, and to report on adverse events associated with their use.
METHODS
We identified systematic reviews examining any opioid for cancer pain published to 4 May 2017 in the Cochrane Database of Systematic Reviews in the Cochrane Library. The primary outcomes were no or mild pain within 14 days of starting treatment, withdrawals due to adverse events, and serious adverse events.
MAIN RESULTS
We included nine reviews with 152 included studies and 13,524 participants, but because some studies appeared in more than one review the number of unique studies and participants was smaller than this. Most participants had moderate or severe pain associated with a range of different types of cancer. Studies in the reviews typically compared one type of opioid or formulation with either a different formulation of the same opioid, or a different opioid; few included a placebo control. Typically the reviews titrated dose to effect, a balance between pain relief and adverse events. Various routes of administration of opioids were considered in the reviews; oral with most opioids, but transdermal administration with fentanyl, and buprenorphine. No review included studies of subcutaneous opioid administration. Pain outcomes reported were varied and inconsistent. The average size of included studies varied considerably between reviews: studies of older opioids, such as codeine, morphine, and methadone, had low average study sizes while those involving newer drugs tended to have larger study sizes.Six reviews reported a GRADE assessment (buprenorphine, codeine, hydromorphone, methadone, oxycodone, and tramadol), but not necessarily for all comparisons or outcomes. No comparative analyses were possible because there was no consistent placebo or active control. Cohort outcomes for opioids are therefore reported, as absolute numbers or percentages, or both.Reviews on buprenorphine, codeine with or without paracetamol, hydromorphone, methadone, tramadol with or without paracetamol, tapentadol, and oxycodone did not have information about the primary outcome of mild or no pain at 14 days, although that on oxycodone indicated that average pain scores were within that range. Two reviews, on oral morphine and transdermal fentanyl, reported that 96% of 850 participants achieved that goal.Adverse event withdrawal was reported by five reviews, at rates of between 6% and 19%. Participants with at least one adverse event were reported by three reviews, at rates of between 11% and 77%.Our GRADE assessment of evidence quality was very low for all outcomes, because many studies in the reviews were at high risk of bias from several sources, including small study size.
AUTHORS' CONCLUSIONS
The amount and quality of evidence around the use of opioids for treating cancer pain is disappointingly low, although the evidence we have indicates that around 19 out of 20 people with moderate or severe pain who are given opioids and can tolerate them should have that pain reduced to mild or no pain within 14 days. This accords with the clinical experience in treating many people with cancer pain, but overstates to some extent the effectiveness found for the WHO pain ladder. Most people will experience adverse events, and help may be needed to manage the more common undesirable adverse effects such as constipation and nausea. Perhaps between 1 in 10 and 2 in 10 people treated with opioids will find these adverse events intolerable, leading to a change in treatment.
Topics: Acetaminophen; Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Buprenorphine; Cancer Pain; Codeine; Fentanyl; Humans; Hydromorphone; Methadone; Oxycodone; Phenols; Review Literature as Topic; Tapentadol; Tramadol
PubMed: 28683172
DOI: 10.1002/14651858.CD012592.pub2