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Environmental Health Perspectives Oct 2014In contrast to current methods of expert-based narrative review, the Navigation Guide is a systematic and transparent method for synthesizing environmental health... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In contrast to current methods of expert-based narrative review, the Navigation Guide is a systematic and transparent method for synthesizing environmental health research from multiple evidence streams. The Navigation Guide was developed to effectively and efficiently translate the available scientific evidence into timely prevention-oriented action.
OBJECTIVES
We applied the Navigation Guide systematic review method to answer the question "Does fetal developmental exposure to perfluorooctanoic acid (PFOA) or its salts affect fetal growth in animals ?" and to rate the strength of the experimental animal evidence.
METHODS
We conducted a comprehensive search of the literature, applied prespecified criteria to the search results to identify relevant studies, extracted data from studies, obtained additional information from study authors, conducted meta-analyses, and rated the overall quality and strength of the evidence.
RESULTS
Twenty-one studies met the inclusion criteria. From the meta-analysis of eight mouse gavage data sets, we estimated that exposure of pregnant mice to increasing concentrations of PFOA was associated with a change in mean pup birth weight of -0.023 g (95% CI: -0.029, -0.016) per 1-unit increase in dose (milligrams per kilogram body weight per day). The evidence, consisting of 15 mammalian and 6 nonmammalian studies, was rated as "moderate" and "low" quality, respectively.
CONCLUSION
Based on this first application of the Navigation Guide methodology, we found sufficient evidence that fetal developmental exposure to PFOA reduces fetal growth in animals.
Topics: Animals; Birth Weight; Caprylates; Environmental Health; Environmental Pollutants; Evidence-Based Medicine; Female; Fetal Development; Fluorocarbons; Mice; Pregnancy
PubMed: 24968374
DOI: 10.1289/ehp.1307177 -
The Cochrane Database of Systematic... Dec 2018Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia....
BACKGROUND
Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia. Atypical endometrial hyperplasia suggests a significant pre-malignant state with frank progression to endometrial carcinoma, and tends to occur at a young age. Oral progestins have been used as conservative treatment in young women with atypical endometrial hyperplasia, but they are associated with poor tolerability and side effects that may limit their overall efficacy. So it has become increasingly important and necessary to find a safe and effective fertility-sparing treatment with better tolerability and fewer side effects than the options currently available. The levonorgestrel-releasing intrauterine system (LNG-IUS) has been used to provide endometrial protection in women with breast cancer who are on adjuvant tamoxifen. The antiproliferative function of levonorgestrel is thought to reduce the risk of endometrial hyperplasia.
OBJECTIVES
To determine the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.
SEARCH METHODS
In July 2018 we searched CENTRAL; MEDLINE; Embase; CINAHL, PsycINFO and the China National Knowledge Infrastructure for relevant trials. Cochrane Gynaecology and Fertility (CGF) Specialised Register and Embase were searched in November 2018. We attempted to identify trials from references in published studies. We also searched for ongoing trials in five major clinical trials registries.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of oral and intrauterine progestogens (LNG-IUS) versus each other or placebo in women with a confirmed histological diagnosis of simple or complex endometrial hyperplasia with atypia.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trial eligibility and risk of bias and extracted the data. The primary outcomes of the review were rate of regression and adverse effects. Secondary outcomes included rate of recurrence and proportion of women undergoing hysterectomy. We have used GRADE methodology to judge the quality of the evidence.
MAIN RESULTS
We included one RCT (153 women) comparing the LNG-IUS administering 20 micrograms (μu) levonorgestrel per day versus 10 milligrams of continuous or cyclical oral medroxyprogesterone (MPA) for treating any type of endometrial hyperplasia. Only 19 women in this study were histologically confirmed with atypical complex hyperplasia before treatment. The evidence was of low or very low quality. The included study was at low risk of bias, but the quality of the evidence was very seriously limited by imprecision and indirectness. We did not find any RCTS comparing the LNG-IUS or oral progestogens versus placebo in women with atypical endometrial hyperplasia.Among the 19 women with atypical complex hyperplasia, after six months of treatment there was insufficient evidence to determine whether there was a difference in regression rates between the LNG-IUS group and the progesterone group (odds ratio (OR) 2.76, 95% confidence interval (CI) 0.26 to 29.73; 1 RCT subgroup, 19 women, very low-quality evidence). The rate of regression was 100% in the LNG-IUS group (n = 6/6) and 77% in the progesterone group (n = 10/13).Among the total study population (N = 153), over the six months' treatment the main adverse effects were nausea and vaginal bleeding. There was no evidence of a difference between the groups in rates of nausea (OR 0.58, 95% CI 0.28 to 1.18; 1 RCT, 153 women, very low-quality evidence). Vaginal bleeding was more common in the LNG-IUS group (OR 2.89, 95% CI 1.11 to 7.52; 1 RCT, 153 women, low-quality evidence). Except for nausea and vaginal bleeding, no other adverse effects were reported.
AUTHORS' CONCLUSIONS
We did not find any RCTS of women with atypical endometrial hyperplasia, and our findings derive from a subgroup of 19 women in a larger RCT. All six women who used the LNG-IUS system achieved regression of atypical hyperplasia, but there was insufficient evidence to draw any conclusions regarding the relative efficacy of LNG-IUS versus oral progesterone (MPA) in this group of women. When assessed in a population of women with any type of endometrial hyperplasia, there was no clear evidence of a difference between LNG-IUS and oral progesterone (MPA) in risk of nausea, but vaginal bleeding was more likely to occur in women using the LNG-IUS. Larger studies are necessary to assess the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.
Topics: Administration, Oral; Endometrial Hyperplasia; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone; Randomized Controlled Trials as Topic
PubMed: 30521671
DOI: 10.1002/14651858.CD009458.pub3 -
Sports Health 2020The prescription of opioids after elective surgical procedures has been a contributing factor to the current opioid epidemic in North America.
CONTEXT
The prescription of opioids after elective surgical procedures has been a contributing factor to the current opioid epidemic in North America.
OBJECTIVE
To examine the opioid prescribing practices and rates of opioid consumption among patients undergoing common sports medicine procedures.
DATA SOURCES
A systematic review of the electronic databases EMBASE, MEDLINE, and PubMed was performed from database inception to December 2018.
STUDY SELECTION
Two investigators independently identified all studies reporting on postoperative opioid prescribing practices and consumption after arthroscopic shoulder, knee, or hip surgery. A total of 119 studies were reviewed, with 8 meeting eligibility criteria.
STUDY DESIGN
Systematic review.
LEVEL OF EVIDENCE
Level 4.
DATA EXTRACTION
The quantity of opioids prescribed and used were converted to milligram morphine equivalents (MMEs) for standardized reporting. The quality of each eligible study was evaluated using the Methodological Index for Non-Randomized Studies.
RESULTS
A total of 8 studies including 816 patients with a mean age of 43.8 years were eligible for inclusion. A mean of 610, 197, and 613 MMEs were prescribed to patients after arthroscopic procedures of the shoulder, knee, and hip, respectively. At final follow-up, 31%, 34%, and 64% of the prescribed opioids provided after shoulder, knee, and hip arthroscopy, respectively, still remained. The majority of patients (64%) were unaware of the appropriate disposal methods for surplus medication. Patients undergoing arthroscopic rotator cuff repair had the highest opioid consumption (471 MMEs), with 1 in 4 patients receiving a refill.
CONCLUSION
Opioids are being overprescribed for arthroscopic procedures of the shoulder, knee, and hip, with more than one-third of prescribed opioids remaining postoperatively. The majority of patients are unaware of the appropriate disposal techniques for surplus opioids. Appropriate risk stratification tools and evidence-based recommendations regarding pain management strategies after arthroscopic procedures are needed to help curb the growing opioid crisis.
Topics: Analgesics, Opioid; Arthroscopy; Athletic Injuries; Hip Injuries; Humans; Knee Injuries; Pain Management; Pain, Postoperative; Practice Patterns, Physicians'; Prescription Drug Overuse; Shoulder Injuries
PubMed: 32271136
DOI: 10.1177/1941738120913293 -
The Western Journal of Emergency... May 2020In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200...
In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200 countries, leading to over 1.6 million cases and over 99,000 deaths. Given that there is neither a vaccine nor proven treatment for COVID-19, there is currently an urgent need for effective pharmacotherapy. To address the need for an effective treatment of SARS-CoV-2 during the worldwide pandemic, this systematic review of intravenous (IV) remdesivir was performed. Remdesivir, an anti-viral prodrug originally developed to treat Ebola virus disease, has shown broad spectrum activity against the Coronavirus family. A recent case report reported improvement of clinical symptoms with remdesivir in a patient with COVID-19. After conducting a systematic search of 18 clinical trial registries and three large scientific databases, we identified 86 potentially eligible items. Following removal of duplicates (n = 21), eligible studies were reviewed independently by two authors. After the first round of screening, inter-rater agreement was 98.5% (κ = 0.925). After the second round of full-text screening, inter-rater agreement was 100%. A total of seven ongoing and recruiting clinical trials of remdesivir (100-200 milligrams, intravenous [IV]) were included. We identified the following primary outcomes: patients discharged (n = 2); time to clinical status improvement (n = 2); improved O2 saturation (n = 2); body temperature normalization (n = 2); and clinical status (n = 1). Secondary outcomes in all identified studies included documentation of adverse events. Phase 3 trials are expected to be completed between April 2020-2023. Therefore, despite supportive data from in vitro and in vivo studies, the clinical effectiveness of IV remdesivir for treatment of COVID-19 and potential side effects remain incompletely defined in the human population.
Topics: Adenosine Monophosphate; Administration, Intravenous; Alanine; Antiviral Agents; Betacoronavirus; COVID-19; Clinical Trials as Topic; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32726230
DOI: 10.5811/westjem.2020.5.47658 -
The Cochrane Database of Systematic... Apr 2012This review is an update of a previously published review in the Cochrane Database of Systematic Reviews on 'Single dose oral aspirin for acute pain'. Aspirin has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is an update of a previously published review in the Cochrane Database of Systematic Reviews on 'Single dose oral aspirin for acute pain'. Aspirin has been known for many years to be an effective analgesic for many different pain conditions. Although its use as an analgesic is now limited in developed countries, it is widely available, inexpensive, and remains commonly used throughout the world.
OBJECTIVES
To assess the analgesic efficacy and associated adverse events of single dose oral aspirin in acute postoperative pain.
SEARCH METHODS
For the earlier review, we identified randomised trials by searching CENTRAL (The Cochrane Library) (1998, Issue 1), MEDLINE (1966 to March 1998), EMBASE (1980 to January 1998), and the Oxford Pain Relief Database (1950 to 1994). We updated searches of CENTRAL, MEDLINE, and EMBASE to January 2012.
SELECTION CRITERIA
Single oral dose, randomised, double-blind, placebo-controlled trials of aspirin for relief of established moderate to severe postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
We assessed studies for methodological quality and two review authors extracted the data independently. We used summed total pain relief (TOTPAR) over four to six hours to calculate the number of participants achieving at least 50% pain relief. We used these derived results to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over four to six hours. We sought numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, as additional measures of efficacy. We collected information on adverse events and withdrawals.
MAIN RESULTS
We included 68 studies in which aspirin was used at doses from 300 mg to 1200 mg, but the vast majority of participants received either 600/650 mg (2409 participants, 64 studies) or 990/1000 mg (380 participants, eight studies). There was only one new study.Studies were overwhelmingly of adequate or good methodological quality. NNTs for at least 50% pain relief over four to six hours were 4.2 (3.9 to 4.8), 3.8 (3.0 to 5.1), and 2.7 (2.0 to 3.8) for 600/650 mg, 900/1000 mg, and 1200 mg respectively, compared with placebo. Type of pain model had no significant impact on the results. Lower doses were not significantly different from placebo. These results do not differ from those of the earlier review.Fewer participants required rescue medication with aspirin than with placebo over four to eight hours postdose, but by 12 hours there was no difference. The number of participants experiencing adverse events was not significantly different from placebo for 600/650 mg aspirin, but for 900/1000 mg the number needed to treat to harm was 7.5 (4.8 to 17). The most commonly reported events were dizziness, drowsiness, gastric irritation, nausea, and vomiting, nearly all of which were of mild to moderate severity.
AUTHORS' CONCLUSIONS
Aspirin is an effective analgesic for acute pain of moderate to severe intensity. High doses are more effective, but are associated with increased adverse events, including drowsiness and gastric irritation. The pain relief achieved with aspirin was very similar milligram for milligram to that seen with paracetamol. There was no change to the conclusions in this update.
Topics: Acute Disease; Administration, Oral; Adult; Analgesics, Non-Narcotic; Aspirin; Humans; Pain, Postoperative
PubMed: 22513905
DOI: 10.1002/14651858.CD002067.pub2 -
The Journal of Trauma and Acute Care... Feb 2022Opioids have been proven effective in pain management, but overprescription can lead to addiction and abuse. Although current guidelines regarding opioid prescription...
BACKGROUND
Opioids have been proven effective in pain management, but overprescription can lead to addiction and abuse. Although current guidelines regarding opioid prescription for chronic and acute pain are available, they fail to address the use of opioids for pain management in traumatic injury patients who undergo operations. The primary objective of this study was to examine opioid prescribing practices for US adult trauma patients who require surgical management, based on prior history of opioid use, type of surgical practice, and age.
METHODS
PubMed and Cochrane Journals were used to identify relevant articles between October 2010 and December 29, 2020. Our primary outcome was discrepancies of morphine milligram equivalents (MMEs) prescribed to trauma patients. Significance was defined as p < 0.05.
RESULTS
Eleven studies on US trauma patients prescribed opioids were evaluated, creating a total of 30,249 patients stratified by prior opioid use, age, and race. Patterns seen among patients with prior opioid use include higher MMEs prescribed, lower likelihoods of opioid discontinuation, higher mortality rates, and higher complication rates. Orthopedic surgeons prescribed higher values of MMEs than nonorthopedic surgeons.
CONCLUSION
Higher incidences of opioid prescriptions are seen with orthopedic trauma surgery and prior opioid use by the patient. We recommend further development of national protocol implementation for acute pain management for the US trauma population.
LEVEL OF EVIDENCE
Systematic review, level III.
Topics: Adult; Analgesics, Opioid; Humans; Pain Management; Pain, Postoperative; Practice Patterns, Physicians'; United States; Wounds and Injuries
PubMed: 34238859
DOI: 10.1097/TA.0000000000003341 -
BMC Anesthesiology Jun 2022Systematic reviews associate peripheral nerve blocks based on anatomic landmarks or nerve stimulation with reduced pain and need for systemic analgesia in hip fracture... (Meta-Analysis)
Meta-Analysis
Systematic reviews associate peripheral nerve blocks based on anatomic landmarks or nerve stimulation with reduced pain and need for systemic analgesia in hip fracture patients. We aimed to investigate the effect of ultrasound-guided nerve blocks compared to conventional analgesia for preoperative pain management in hip fractures. Five databases were searched until June 2021 to identify randomised controlled trials. Two independent authors extracted data and assessed risk of bias. Data was pooled for meta-analysis and quality of evidence was evaluated using Grades of Recommendation Assessment, Development and Evaluation (GRADE). We included 12 trials (976 participants) comparing ultrasound-guided nerve blocks to conventional systemic analgesia. In favour of ultrasound, pain measured closest to two hours after block placement decreased with a mean difference of -2.26 (VAS 0 to 10); (p < 0.001) 95% CI [-2.97 to -1.55]. In favour of ultrasound, preoperative analgesic usage of iv. morphine equivalents in milligram decreased with a mean difference of -5.34 (p=0.003) 95% CI [-8.11 to -2.58]. Time from admission until surgery ranged from six hours to more than three days. Further, ultrasound-guided nerve blocks may be associated with a lower frequency of delirium: risk ratio 0.6 (p = 0.03) 95% CI [0.38 to 0.94], fewer serious adverse events: risk ratio 0.33 (p = 0.006) 95% CI [0.15 to 0.73] and higher patient satisfaction: mean difference 25.9 (VAS 0 to 100) (p < 0.001) 95% CI [19.74 to 32.07]. However, the quality of evidence was judged low or very low. In conclusion, despite low quality of evidence, ultrasound-guided blocks were associated with benefits compared to conventional systemic analgesia.
Topics: Hip Fractures; Humans; Pain; Pain Management; Pain, Postoperative; Peripheral Nerves; Ultrasonography, Interventional
PubMed: 35729489
DOI: 10.1186/s12871-022-01720-7 -
The Cochrane Database of Systematic... Apr 1996People with nonrheumatic atrial fibrillation who have had a transient ischemic attack or minor ischemic stroke are at risk of recurrent stroke. (Review)
Review
BACKGROUND
People with nonrheumatic atrial fibrillation who have had a transient ischemic attack or minor ischemic stroke are at risk of recurrent stroke.
OBJECTIVES
The objective of this review was to assess the effect of antiplatelet therapy for secondary prevention in people with nonrheumatic atrial fibrillation and a previous transient ischaemic attack or ischaemic stroke.
SEARCH STRATEGY
The reviewer searched the Cochrane Stroke Group trials register and contacted trialists.
SELECTION CRITERIA
Randomised trials comparing an antiplatelet agent with placebo or open control in people with nonrheumatic atrial fibrillation and a previous transient ischaemic attack or minor ischaemic stroke.
DATA COLLECTION AND ANALYSIS
One reviewer extracted the data.
MAIN RESULTS
One trial was included, in which 300 milligrams of aspirin per day was compared with placebo. This review includes 404 aspirin-treated patients and 378 placebo patients in total. The mean follow-up was 2.3 years. No difference was shown between aspirin and placebo in the annual rate of all vascular events, including vascular death, recurrent stroke (ischaemic or haemorrhagic), myocardial infarction, and systemic embolism. The odds ratio was 0.84, 95% confidence interval 0.63 to 1.14, or 15% of those receiving aspirin versus 19% for those given placebo. Aspirin may prevent 40 vascular events (of all types) per 1000 patients treated for one year. There was a non-significant reduction in the risk of recurrent stroke from 12% to 10% per year (odds ratio 0.89, 95% confidence interval 0.64 to 1.24). The incidence of major bleeding events, requiring hospitalisation, blood transfusion or surgical treatment, was low (0.9% per year for aspirin versus 0.7% for placebo).
AUTHORS' CONCLUSIONS
Aspirin may reduce the risk of vascular events in people with nonrheumatic atrial fibrillation, but the effect shown in the single trial was not statistically significant.
Topics: Atrial Fibrillation; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke
PubMed: 17636615
DOI: 10.1002/14651858.CD000186.pub2 -
The Cochrane Database of Systematic... 2000People with nonrheumatic atrial fibrillation who have had a transient ischemic attack or minor ischemic stroke are at risk of recurrent stroke. (Review)
Review
BACKGROUND
People with nonrheumatic atrial fibrillation who have had a transient ischemic attack or minor ischemic stroke are at risk of recurrent stroke.
OBJECTIVES
The objective of this review was to assess the effect of antiplatelet therapy for secondary prevention in people with nonrheumatic atrial fibrillation and a previous transient ischaemic attack or ischaemic stroke.
SEARCH STRATEGY
The reviewer searched the Cochrane Stroke Group trials register and contacted trialists.
SELECTION CRITERIA
Randomised trials comparing an antiplatelet agent with placebo or open control in people with nonrheumatic atrial fibrillation and a previous transient ischaemic attack or minor ischaemic stroke.
DATA COLLECTION AND ANALYSIS
One reviewer extracted the data.
MAIN RESULTS
One trial was included, in which 300 milligrams of aspirin per day was compared with placebo. This review includes 404 aspirin-treated patients and 378 placebo patients in total. The mean follow-up was 2.3 years. No difference was shown between aspirin and placebo in the annual rate of all vascular events, including vascular death, recurrent stroke (ischaemic or haemorrhagic), myocardial infarction, and systemic embolism. The odds ratio was 0.84, 95% confidence interval 0.63 to 1. 14, or 15% of those receiving aspirin versus 19% for those given placebo. Aspirin may prevent 40 vascular events (of all types) per 1000 patients treated for one year. There was a non-significant reduction in the risk of recurrent stroke from 12% to 10% per year (odds ratio 0.89, 95% confidence interval 0.64 to 1.24). The incidence of major bleeding events, requiring hospitalisation, blood transfusion or surgical treatment, was low (0.9% per year for aspirin versus 0.7% for placebo).
REVIEWER'S CONCLUSIONS
Aspirin may reduce the risk of vascular events in people with nonrheumatic atrial fibrillation, but the effect shown in the single trial was not statistically significant.
Topics: Atrial Fibrillation; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke
PubMed: 10796314
DOI: 10.1002/14651858.CD000186 -
Pain Physician Nov 2019Opioid medications are frequently used effectively for analgesia in acute settings, however, they are associated with dependence and addiction, and were implicated in...
BACKGROUND
Opioid medications are frequently used effectively for analgesia in acute settings, however, they are associated with dependence and addiction, and were implicated in 47,600 American fatalities in 2017. Evidence suggests that despite guidelines and professional body recommendations, acute prescribing remains highly variable. Educational interventions targeting prescribers have potential to optimize prescribing in-line with evidence-based best practice.
OBJECTIVES
To identify the objective impacts of education interventions on opioid prescribing in the acute care setting.
STUDY DESIGN
A systematic literature review.
SETTING
The electronic databases MEDLINE, Embase, and Cochrane for works published until December 31, 2018. Bibliographies of relevant studies and the gray literature were also searched.
METHODS
Databases were searched for interventional studies (clinical trials and pre- and poststudies). Studies describing an educational intervention delivered to clinicians and reporting at least one objective measure of opioid use in the acute care setting were included. Studies reporting only subjective outcomes and those focused on chronic pain or set in primary care were excluded. Two reviewers (RB, TB) extracted data and assessed the quality of included studies using the Downs and Black Tool.
RESULTS
Nine studies met inclusion criteria; all used pre- and postdesigns. Three studies described stand-alone education, and the others described multifaceted interventions. All 9 interventions significantly reduced at least one of the following: high-risk agent use including meperidine use by up to 71%; total or daily dosage of opioids at discharge, including median morphine milligram equivalence (MME) from 90 mg to 45 mg per patient; and quantity of medications such as oxycodone supplied to patients, halved in one study from 6,170 expected to 2,932 supplied tablets. No increase in pain complaints or prescription refill requests were reported in those studies assessing these outcomes. The longest study examined prescribing 15 months after education delivery, reporting sustained practice changes.
LIMITATIONS
Overall study quality was fair to poor. Significant heterogeneity in settings, patient groups, methodologies, and outcomes prevented pooled quantitative analysis. No studies examined all available opioid agents or formulations.
CONCLUSIONS
These findings support prescriber education as an effective strategy to reduce opioid use and optimize prescribing in acute settings. Further research, particularly high quality randomized studies, describing the impact of education on all available opioid formulations and total MME is required. Reviewing the existing literature has offered useful models that can be implemented to improve care with opioid prescribing in acute settings.
KEY WORDS
Opioids, education, physician education, prescriber education, opioid education, opioid prescribing, systematic review, prescriptions, prevention.
Topics: Analgesics, Opioid; Drug Prescriptions; Humans; Opioid-Related Disorders; Oxycodone; Pain; Practice Patterns, Physicians'; Primary Health Care
PubMed: 31775401
DOI: No ID Found