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British Journal of Anaesthesia Jun 2014Opioids can increase sensitivity to noxious stimuli and cause opioid-induced hyperalgesia. We performed a systematic review to evaluate the clinical consequences of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Opioids can increase sensitivity to noxious stimuli and cause opioid-induced hyperalgesia. We performed a systematic review to evaluate the clinical consequences of intra-operative doses of opioid.
METHODS
We identified randomized controlled trials which compared intra-operative opioid to lower doses or placebo in adult patients undergoing surgery from MEDLINE, EMBASE, LILAC, Cochrane, and hand searches of trial registries. We pooled data of postoperative pain intensity, morphine consumption, incidence of opioid-related side-effects, primary and secondary hyperalgesia. For dichotomous outcomes relative risks [95% confidence intervals (CIs)] and for continuous outcomes mean differences (MDs) or standardized mean difference (SMD; 95% CI) were calculated.
RESULTS
Twenty-seven studies involving 1494 patients were included in the analysis. Patients treated with high intra-operative doses of opioid reported higher postoperative pain intensity than the reference groups (MD: 9.4 cm; 95% CI: 4.4, 14.5) at 1 h, (MD: 7.1 cm; 95% CI: 2.8, 11.3) at 4 h, and (MD: 3 cm; 95% CI: 0.4, 5.6) at 24 h on a 100 cm visual analogue scale. They also showed higher postoperative morphine use after 24 h (SMD: 0.7; 95% CI: 0.37, 1.02). There was no difference in the incidences of nausea, vomiting, and drowsiness. These results were mainly associated with the use of remifentanil. The impact of other opioids is less clear because of limited data.
DISCUSSION
This review suggests that high intra-operative doses of remifentanil are associated with small but significant increases in acute pain after surgery.
Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Humans; Hyperalgesia; Pain Measurement; Pain, Postoperative; Piperidines; Randomized Controlled Trials as Topic; Remifentanil
PubMed: 24829420
DOI: 10.1093/bja/aeu137 -
JAMA Internal Medicine Jan 2020Mind-body therapies (MBTs) are emerging as potential tools for addressing the opioid crisis. Knowing whether mind-body therapies may benefit patients treated with... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Mind-body therapies (MBTs) are emerging as potential tools for addressing the opioid crisis. Knowing whether mind-body therapies may benefit patients treated with opioids for acute, procedural, and chronic pain conditions may be useful for prescribers, payers, policy makers, and patients.
OBJECTIVE
To evaluate the association of MBTs with pain and opioid dose reduction in a diverse adult population with clinical pain.
DATA SOURCES
For this systematic review and meta-analysis, the MEDLINE, Embase, Emcare, CINAHL, PsycINFO, and Cochrane Library databases were searched for English-language randomized clinical trials and systematic reviews from date of inception to March 2018. Search logic included (pain OR analgesia OR opioids) AND mind-body therapies. The gray literature, ClinicalTrials.gov, and relevant bibliographies were also searched.
STUDY SELECTION
Randomized clinical trials that evaluated the use of MBTs for symptom management in adults also prescribed opioids for clinical pain.
DATA EXTRACTION AND SYNTHESIS
Independent reviewers screened citations, extracted data, and assessed risk of bias. Meta-analyses were conducted using standardized mean differences in pain and opioid dose to obtain aggregate estimates of effect size with 95% CIs.
MAIN OUTCOMES AND MEASURES
The primary outcome was pain intensity. The secondary outcomes were opioid dose, opioid misuse, opioid craving, disability, or function.
RESULTS
Of 4212 citations reviewed, 60 reports with 6404 participants were included in the meta-analysis. Overall, MBTs were associated with pain reduction (Cohen d = -0.51; 95% CI, -0.76 to -0.26) and reduced opioid dose (Cohen d = -0.26; 95% CI, -0.44 to -0.08). Studies tested meditation (n = 5), hypnosis (n = 25), relaxation (n = 14), guided imagery (n = 7), therapeutic suggestion (n = 6), and cognitive behavioral therapy (n = 7) interventions. Moderate to large effect size improvements in pain outcomes were found for meditation (Cohen d = -0.70), hypnosis (Cohen d = -0.54), suggestion (Cohen d = -0.68), and cognitive behavioral therapy (Cohen d = -0.43) but not for other MBTs. Although most meditation (n = 4 [80%]), cognitive-behavioral therapy (n = 4 [57%]), and hypnosis (n = 12 [63%]) studies found improved opioid-related outcomes, fewer studies of suggestion, guided imagery, and relaxation reported such improvements. Most MBT studies used active or placebo controls and were judged to be at low risk of bias.
CONCLUSIONS AND RELEVANCE
The findings suggest that MBTs are associated with moderate improvements in pain and small reductions in opioid dose and may be associated with therapeutic benefits for opioid-related problems, such as opioid craving and misuse. Future studies should carefully quantify opioid dosing variables to determine the association of mind-body therapies with opioid-related outcomes.
Topics: Analgesics, Opioid; Chronic Pain; Cognitive Behavioral Therapy; Humans; Meditation; Pain Management
PubMed: 31682676
DOI: 10.1001/jamainternmed.2019.4917 -
Pharmacotherapy May 2022Buprenorphine possesses many unique attributes that make it a practical agent for adults and adolescents with opioid use disorder (OUD) and/or acute or chronic pain.... (Review)
Review
Buprenorphine possesses many unique attributes that make it a practical agent for adults and adolescents with opioid use disorder (OUD) and/or acute or chronic pain. Sublingual buprenorphine has been the standard of care for treating OUD, but its use in pain management is not as clearly defined. Current practice guidelines recommend a period of mild-to-moderate withdrawal from opioids before transitioning to buprenorphine due to its ability to displace full agonists from the μ-opioid receptor. However, this strategy can lead to negative physical and psychological outcomes for patients. Novel initiation strategies suggest that concomitant administration of small doses of buprenorphine with opioids can avoid the unwanted withdrawal associated with buprenorphine initiation. We aim to systematically review the buprenorphine initiation strategies that have emerged in the last decade. Embase, PubMed, and Cochrane Databases were searched for relevant literature. Studies were included if they were published in the English language and described the transition to buprenorphine from opioids. Data were collected from each study and synthesized using descriptive statistics. This review included 7 observational studies, 1 feasibility study, and 39 case reports/series which included 924 patients. The strategies utilized between the literature included traditional initiation (47.9%), microdosing with various buprenorphine formulations (16%), and miscellaneous methods (36.1%). Traditional initiation and microdosing initiation were compared in the data synthesis and analysis; miscellaneous methods were omitted given the high variability between methods. Overall, 95.6% of patients in the traditional initiation group and 96% of patients in the microdosing group successfully rotated to sublingual buprenorphine. Initiation regimens can vary widely depending on patient-specific factors and buprenorphine formulation. A variety of buprenorphine transition strategies are published in the literature, many of which were effective for patients with OUD, pain, or both.
Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Observational Studies as Topic; Opioid-Related Disorders; Pain Management
PubMed: 35302671
DOI: 10.1002/phar.2676 -
Pain Apr 2015Opioid use in chronic pain treatment is complex, as patients may derive both benefit and harm. Identification of individuals currently using opioids in a problematic way... (Review)
Review
Opioid use in chronic pain treatment is complex, as patients may derive both benefit and harm. Identification of individuals currently using opioids in a problematic way is important given the substantial recent increases in prescription rates and consequent increases in morbidity and mortality. The present review provides updated and expanded information regarding rates of problematic opioid use in chronic pain. Because previous reviews have indicated substantial variability in this literature, several steps were taken to enhance precision and utility. First, problematic use was coded using explicitly defined terms, referring to different patterns of use (ie, misuse, abuse, and addiction). Second, average prevalence rates were calculated and weighted by sample size and study quality. Third, the influence of differences in study methodology was examined. In total, data from 38 studies were included. Rates of problematic use were quite broad, ranging from <1% to 81% across studies. Across most calculations, rates of misuse averaged between 21% and 29% (range, 95% confidence interval [CI]: 13%-38%). Rates of addiction averaged between 8% and 12% (range, 95% CI: 3%-17%). Abuse was reported in only a single study. Only 1 difference emerged when study methods were examined, where rates of addiction were lower in studies that identified prevalence assessment as a primary, rather than secondary, objective. Although significant variability remains in this literature, this review provides guidance regarding possible average rates of opioid misuse and addiction and also highlights areas in need of further clarification.
Topics: Analgesics, Opioid; Behavior, Addictive; Chronic Pain; Humans; Opioid-Related Disorders; Prevalence; Substance-Related Disorders
PubMed: 25785523
DOI: 10.1097/01.j.pain.0000460357.01998.f1 -
Acta Anaesthesiologica Scandinavica Feb 2022Opioid-based treatment is used to manage stress responses during surgery and postoperative pain. However, opioids have both acute and long-term side effects, calling for... (Meta-Analysis)
Meta-Analysis Review
Total opioid-free general anaesthesia can improve postoperative outcomes after surgery, without evidence of adverse effects on patient safety and pain management: A systematic review and meta-analysis.
BACKGROUND
Opioid-based treatment is used to manage stress responses during surgery and postoperative pain. However, opioids have both acute and long-term side effects, calling for opioid-free anaesthetic strategies. This meta-analysis compares adverse events, postoperative recovery, discharge time from post-anaesthesia care unit, and postoperative pain, nausea, vomiting, and opioid consumption between strict opioid-free and opioid-based general anaesthesia.
METHODS
We conducted a systematic review and meta-analysis. We searched PubMed, Embase, Cinahl, Cochrane Library, selected reference lists, and Google Scholar. We included randomised controlled trials (RCTs) published between January 2000 and February 2021 with at least one opioid-free study arm, i.e. no opioids administered preoperatively, during anaesthesia induction, before skin closure, or before emergence from anaesthesia.
RESULTS
The study comprised 1934 patients from 26 RCTs. Common interventions included laparoscopic gynaecological surgery, upper gastrointestinal surgery, and breast surgery. There is firm evidence that opioid-free anaesthesia significantly reduced adverse postoperative events (OR 0.32, 95% CI 0.22 to 0.46, I = 56%, p < 0.00001), mainly driven by decreased nausea (OR 0.27, (0.17 to 0.42), p < 0.00001) and vomiting (OR 0.22 (0.11 to 0.41), p < 0.00001). Postoperative opioid consumption was significantly lower in the opioid-free group (-6.00 mg (-8.52 to -3.48), p < 0.00001). There was no significant difference in length of post-anaesthesia care unit stay and overall postoperative pain between groups.
CONCLUSIONS
Opioid-free anaesthesia can improve postoperative outcomes in several surgical settings without evidence of adverse effects on patient safety and pain management. There is a need for more evidence-based non-opioid anaesthetic protocols for different types of surgery as well as postoperative phases.
Topics: Analgesics, Opioid; Anesthesia, General; Humans; Pain, Postoperative; Patient Safety
PubMed: 34724195
DOI: 10.1111/aas.13994 -
JAMA Surgery Oct 2017There is increased interest in nonpharmacological treatments to reduce pain after total knee arthroplasty. Yet, little consensus supports the effectiveness of these... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
There is increased interest in nonpharmacological treatments to reduce pain after total knee arthroplasty. Yet, little consensus supports the effectiveness of these interventions.
OBJECTIVE
To systematically review and meta-analyze evidence of nonpharmacological interventions for postoperative pain management after total knee arthroplasty.
DATA SOURCES
Database searches of MEDLINE (PubMed), EMBASE (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, Web of Science (ISI database), Physiotherapy Evidence (PEDRO) database, and ClinicalTrials.gov for the period between January 1946 and April 2016.
STUDY SELECTION
Randomized clinical trials comparing nonpharmacological interventions with other interventions in combination with standard care were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted the data from selected articles using a standardized form and assessed the risk of bias. A random-effects model was used for the analyses.
MAIN OUTCOMES AND MEASURES
Postoperative pain and consumption of opioids and analgesics.
RESULTS
Of 5509 studies, 39 randomized clinical trials were included in the meta-analysis (2391 patients). The most commonly performed interventions included continuous passive motion, preoperative exercise, cryotherapy, electrotherapy, and acupuncture. Moderate-certainty evidence showed that electrotherapy reduced the use of opioids (mean difference, -3.50; 95% CI, -5.90 to -1.10 morphine equivalents in milligrams per kilogram per 48 hours; P = .004; I2 = 17%) and that acupuncture delayed opioid use (mean difference, 46.17; 95% CI, 20.84 to 71.50 minutes to the first patient-controlled analgesia; P < .001; I2 = 19%). There was low-certainty evidence that acupuncture improved pain (mean difference, -1.14; 95% CI, -1.90 to -0.38 on a visual analog scale at 2 days; P = .003; I2 = 0%). Very low-certainty evidence showed that cryotherapy was associated with a reduction in opioid consumption (mean difference, -0.13; 95% CI, -0.26 to -0.01 morphine equivalents in milligrams per kilogram per 48 hours; P = .03; I2 = 86%) and in pain improvement (mean difference, -0.51; 95% CI, -1.00 to -0.02 on the visual analog scale; P < .05; I2 = 62%). Low-certainty or very low-certainty evidence showed that continuous passive motion and preoperative exercise had no pain improvement and reduction in opioid consumption: for continuous passive motion, the mean differences were -0.05 (95% CI, -0.35 to 0.25) on the visual analog scale (P = .74; I2 = 52%) and 6.58 (95% CI, -6.33 to 19.49) opioid consumption at 1 and 2 weeks (P = .32, I2 = 87%), and for preoperative exercise, the mean difference was -0.14 (95% CI, -1.11 to 0.84) on the Western Ontario and McMaster Universities Arthritis Index Scale (P = .78, I2 = 65%).
CONCLUSIONS AND RELEVANCE
In this meta-analysis, electrotherapy and acupuncture after total knee arthroplasty were associated with reduced and delayed opioid consumption.
Topics: Analgesics, Opioid; Arthroplasty, Replacement, Knee; Humans; Pain Management; Pain, Postoperative
PubMed: 28813550
DOI: 10.1001/jamasurg.2017.2872 -
Anaesthesia May 2019Opioids are administered peri-operatively for postoperative analgesia, and intra-operatively to control the sympathetic response to surgical stimuli, frequently as a... (Meta-Analysis)
Meta-Analysis
Opioids are administered peri-operatively for postoperative analgesia, and intra-operatively to control the sympathetic response to surgical stimuli, frequently as a surrogate for presumed pain. However, opioid use during surgery is a matter of dispute in contemporary practice and carries the risk of side-effects such as postoperative nausea and vomiting. This meta-analysis investigated whether opioid-inclusive, compared with opioid-free anaesthesia, would reduce postoperative pain, without increasing the rate of postoperative nausea and vomiting. The electronic databases Medline and PubMed were searched until June 2018. We included trials investigating pain outcomes and comparing any type of intra-operative opioid administration with placebo injection or no intra-operative opioid. Most meta-analyses were performed using a random effects model. We rated the quality of evidence for each outcome. The primary outcome was pain score at rest (analogue scale, 0-10) at two postoperative hours. Our secondary outcomes included the rate of postoperative nausea and vomiting within the first 24 postoperative hours and length of stay in the recovery area. Twenty-three randomised controlled trials, including 1304 patients, were identified. Pain scores at rest at two postoperative hours were equivalent in the opioid-inclusive and opioid-free groups with a mean difference (95%CI) of 0.2 (-0.2 to 0.5), I = 83%, p = 0.38 and a high quality of evidence. Similarly, there was high-quality evidence that the rate of postoperative nausea and vomiting was reduced in the opioid-free group, with a risk ratio (95%CI) of 0.77 (0.61-0.97), I = 16%, p = 0.03 and high-quality evidence for a similar length of stay in the recovery area, the mean difference (95%CI) being 0.6 (-8.2 to 9.3), min, I = 60%, p = 0.90. As there is strong evidence that opioid-inclusive anaesthesia does not reduce postoperative pain, but is associated with more postoperative nausea and vomiting, when compared with opioid-free anaesthesia, we suggest that anaesthetists should reconsider their intra-operative opioid choices on a case-by-case basis.
Topics: Analgesics, Opioid; Anesthesia, General; Drug Administration Schedule; Humans; Intraoperative Care; Pain, Postoperative; Postoperative Nausea and Vomiting
PubMed: 30802933
DOI: 10.1111/anae.14582 -
JAMA Dec 2018Harms and benefits of opioids for chronic noncancer pain remain unclear. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Harms and benefits of opioids for chronic noncancer pain remain unclear.
OBJECTIVE
To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain.
DATA SOURCES AND STUDY SELECTION
The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control.
DATA EXTRACTION AND SYNTHESIS
Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence.
MAIN OUTCOMES AND MEASURES
The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting.
RESULTS
Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], -0.69 cm [95% CI, -0.82 to -0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low- to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, -0.60 cm [95% CI, -1.54 to 0.34 cm]; physical functioning: WMD, -0.90 points [95% CI, -2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, -0.13 cm [95% CI, -0.99 to 0.74 cm]; physical functioning: WMD, -5.31 points [95% CI, -13.77 to 3.14 points]), and anticonvulsants (pain: WMD, -0.90 cm [95% CI, -1.65 to -0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, -5.77 to 6.66 points]).
CONCLUSIONS AND RELEVANCE
In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.
Topics: Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antidepressive Agents, Tricyclic; Cannabinoids; Chronic Pain; Female; Humans; Male; Middle Aged; Pain Measurement; Randomized Controlled Trials as Topic; Vomiting
PubMed: 30561481
DOI: 10.1001/jama.2018.18472 -
Journal of the American Medical... Apr 2018The use of psychotropic medication and cardiovascular medication has been associated with an increased risk of falling. However, other frequently prescribed medication... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The use of psychotropic medication and cardiovascular medication has been associated with an increased risk of falling. However, other frequently prescribed medication classes are still under debate as potential risk factors for falls in the older population. The aim of this systematic review and meta-analysis is to evaluate the associations between fall risk and nonpsychotropic and noncardiovascular medications.
METHODS AND DESIGN
A systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated nonpsychotropic and noncardiovascular medications as risk factors for falls in participants ≥60 years or participants with a mean age ≥70 years. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratio (OR) estimates separately.
RESULTS
In a qualitative synthesis, 281 studies were included. The results of meta-analysis using adjusted data were as follows (a pooled OR [95% confidence interval]): analgesics, 1.42 (0.91-2.23); nonsteroidal anti-inflammatory drugs (NSAIDs), 1.09 (0.96-1.23); opioids, 1.60 (1.35-1.91); anti-Parkinson drugs, 1.54 (0.99-2.39); antiepileptics, 1.55 (1.25-1.92); and polypharmacy, 1.75 (1.27-2.41). Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and setting in most cases. In a descriptive synthesis, consistent associations with falls were observed for long-term proton pump inhibitor use and opioid initiation. Laxatives showed inconsistent associations with falls (7/20 studies showing a positive association).
CONCLUSION
Opioid and antiepileptic use and polypharmacy were significantly associated with increased risk of falling in the meta-analyses. Long-term use of proton pump inhibitors and opioid initiation might increase the fall risk. Future research is necessary because the causal role of some medication classes as fall-risk-increasing drugs remains unclear, and the existing literature contains significant limitations.
Topics: Accidental Falls; Age Factors; Aged; Aged, 80 and over; Analgesics, Opioid; Antidepressive Agents; Benzodiazepines; Female; Humans; Incidence; Male; Middle Aged; Netherlands; Psychotropic Drugs; Public Health; Risk Assessment; Sex Factors
PubMed: 29402646
DOI: 10.1016/j.jamda.2017.12.099 -
Lancet (London, England) Oct 2019We summarise the evidence for medicinal uses of opioids, harms related to the extramedical use of, and dependence on, these drugs, and a wide range of interventions used...
We summarise the evidence for medicinal uses of opioids, harms related to the extramedical use of, and dependence on, these drugs, and a wide range of interventions used to address these harms. The Global Burden of Diseases, Injuries, and Risk Factors Study estimated that in 2017, 40·5 million people were dependent on opioids (95% uncertainty interval 34·3-47·9 million) and 109 500 people (105 800-113 600) died from opioid overdose. Opioid agonist treatment (OAT) can be highly effective in reducing illicit opioid use and improving multiple health and social outcomes-eg, by reducing overall mortality and key causes of death, including overdose, suicide, HIV, hepatitis C virus, and other injuries. Mathematical modelling suggests that scaling up the use of OAT and retaining people in treatment, including in prison, could avert a median of 7·7% of deaths in Kentucky, 10·7% in Kiev, and 25·9% in Tehran over 20 years (compared with no OAT), with the greater effects in Tehran and Kiev being due to reductions in HIV mortality, given the higher prevalence of HIV among people who inject drugs in those settings. Other interventions have varied evidence for effectiveness and patient acceptability, and typically affect a narrower set of outcomes than OAT does. Other effective interventions focus on preventing harm related to opioids. Despite strong evidence for the effectiveness of a range of interventions to improve the health and wellbeing of people who are dependent on opioids, coverage is low, even in high-income countries. Treatment quality might be less than desirable, and considerable harm might be caused to individuals, society, and the economy by the criminalisation of extramedical opioid use and dependence. Alternative policy frameworks are recommended that adopt an approach based on human rights and public health, do not make drug use a criminal behaviour, and seek to reduce drug-related harm at the population level.
Topics: Analgesics, Opioid; Drug Overdose; Global Health; Health Knowledge, Attitudes, Practice; Humans; Opioid-Related Disorders; Prevalence; Risk Factors
PubMed: 31657732
DOI: 10.1016/S0140-6736(19)32229-9