The abstract, “Overprescription of Opioids in White Children from Higher Socioeconomic Backgrounds: Disparities in Opioid Utilization for Pediatric Supracondylar Humerus Fractures,” looked at the rates in opioid prescriptions following childhood broken elbow diagnoses from 2012 to 2021.

Apurva Shah, MD, MBA, Attending Surgeon, Orthopaedic Surgery at the Children’s Hospital of Philadelphia, who authored the abstract, also pointed to results that showed a third of patients in the abstract received at least one opioid dose during their visit.

“As orthopaedic surgeons, we clearly need improved opioid use stewardship to improve healthcare outcomes for our patients,” Dr. Shah said.

Results found disparities in patient racial backgrounds, with Black children 27% less likely to receive an opioid prescription compared to other patients. By comparison, white patients were also shown to be 10% more likely to be given opioids.

Other factors that impacted patients’ likelihood of being given opioids included age and where they live, according to Dr. Shah.

“Non-opioid pain management has proven sufficient for pain management,” Dr. Shah said. “Knowing this, along with this abstract, pediatricians must consider the potential harm these drugs can have on populations with disproportionately easier access to healthcare.”

This research was funded by Children’s Hospital of Philadelphia, Division of Orthopaedics.

Scott Mahon is scheduled to present the research, which is below, at 8:51 – 8:55  a.m. on Sunday, Sept. 29 during the Section on Orthopaedics program at Orange County Convention Center, West Building, W311H. To request an interview with the authors, contact Ashley Moore at moorea1@chop.edu.

The American Academy of Pediatrics is an organization of 67,000 primary care pediatricians, pediatric medical subspecialists and pediatric surgical specialists dedicated to the health, safety and well-being of infants, children, adolescents and young adults. For more information, visit www.aap.org. Reporters can access the meeting program and other relevant meeting information through the AAP meeting website at http://www.aapexperience.org/ 

ABSTRACT

Program Name: 2024 AAP National Conference-Abstracts

Submission Type: Section on Orthopaedics

Abstract Title: Overprescription of Opioids in White Children from Higher Socioeconomic Backgrounds: Disparities in Opioid Utilization for Pediatric Supracondylar Humerus Fractures

Apurva Shah

Philadelphia, PA, United States

In November 2019, the Australian National Prescribing Service launched a federal initiative to improve opioid prescribing.  The initiative involved alerting high-prescribing clinicians that their opioid prescribing practices were outside typical ranges for that practitioner group (2019), providing training in opioid prescribing (2019), reducing the oxycodone package size (2020), and adding warning messages to oxycodone packaging (2020).

The study used wastewater-based epidemiology to estimate the quantity of oxycodone consumed by a community by sampling the community’s sewage as it flowed into a wastewater facility and measuring the levels of oxycodone and its metabolite, noroxycodone, excreted in urine.

For this study, the Australian National Wastewater Drug Monitoring program (NWDMP) collected and analysed 6,999 samples from over 50 wastewater treatment plants across Australia from April 2017 to April 2023.  The results of the analysis are listed below.

• Oxycodone use initially increased from 78 mg/day/1000 people in April 2017 to 120 mg/day/1000 people in August 2019.  This 52% increase occurred before the federal initiative to improve opioid prescribing began.
• Oxycodone use then decreased from 120 mg/day/1000 people in August 2019 to 65 mg/day/1000 people in December 2020.  This 45% decrease coincided with the introduction of prescribing guidelines in 2019 and oxycodone packaging changes in 2020.
• Oxycodone use showed a minor 2.4% increase from December 2020 to April 2023.

Lead author Dr. Rory Verhagen from UQ’s Queensland Alliance for Environmental Health Sciences explains, “The main finding from this study was that a big reduction in oxycodone use between 2019 and 2020 coincided with the introduction of national clinical and regulatory changes intended to reduce pharmaceutical opioid use.  It is likely that the combination of smaller package sizes and educational initiatives in 2019 and early 2020 reduced consumption of oxycodone in Australia.”

The reduction in oxycodone use has not been offset by an increase in heroin or fentanyl use in Australia.  NWDMP monitoring shows that throughout the study period, the consumption of heroin fluctuated without any clear trend while fentanyl followed a similar trend to oxycodone.

The study was conducted by researchers from The University of Queensland, the University of South Australia, and Queensland Health, Australia with primary funding from the Australian Criminal Intelligence Commission; it appears in the scientific journal Addiction.

Full citation for article: Verhagen R, Gerber C, Thai PK, Connor J, Loveday B, Bade R, O’Brien J, Jaunay EL, Simpson BS, Chan G, Hall W, Thomas KV, Mueller JF, Tscharke BJ.  Wastewater-based evaluation of the efficacy of oxycodone regulations in Australia. Addiction. 2024. DOI: 10.1111/add.16653.

Primary funding: The Australian Criminal Intelligence Commission and Queensland Health Australia provided financial support for this research.  Wastewater catchment mapping and sampling was conducted under an Australian Research Council Linkage Project (LP190101124, LP220100058).

Declaration of interests: None.

Why is opioid use before hip or knee replacement a problem?

Patients who require THA or TKA suffer from end stage osteoarthritis with chronic pain. Opioids often provide no better pain relief that simple analgesics and yet they carry the risk of additional side effects such as drowsiness and the risk of falls. Moreover, opioid use before surgery is linked to worse outcomes including slower recovery and persistent opioid use three months after surgery.

THA and TKA are among the most common elective surgical procedures performed around the world and numbers are expected to at least double over the next decade.

The OpioidHALT trial (Feasibility of responsible pre-operative opioid use for Hip and knee ArthropLasTy (OpioidHALT) pilot study) was designed to examine the feasibility and acceptability of an intervention to reduce opioid use before elective THA or TKA compared to usual practice.

How OpioidHALT tackles pre-operative opioid use?

There is little published evidence for the effectiveness of opioid dose tapering. One previous retrospective study showed that patients who tapered their opioids before surgery might have better post-surgical outcomes. However, as the study was not randomised it was not known if there was something different about the patients who tapered their doses.

The OpioidHALT study involved video or telephone consultations with a pharmacist starting three months before the date of the operation. The pharmacist worked with each patient to develop an opioid tapering plan that was evaluated for safety by a pain specialist. Patients determined the level of opioid tapering that they wished within the framework of national guidelines i.e. 10 to 25% of the patient’s baseline opioid dose tapered per month.

What the OpioidHALT pilot study tells us

The initial consultations in the OpioidHALT study took about one hour. Follow-up appointments started one week after each dose reduction and were typically shorter, Patients were educated about how to identify and manage opioid withdrawal symptoms. “If necessary, the patient was put back on a higher opioid dose”, says Dr Liu.

OpioidHALT was a pilot study designed to determine whether the intervention delivered by pharmacists led to successful tapering of opioid doses. The results showed that in the intervention group 90% of patients tapered their opioid doses by at least 50% before surgery compared with17% in the usual care group.

Although the pilot study was not powered to evaluate other outcomes, some of the emerging findings suggest important impacts. In the intervention group there were –

• Fewer opioids consumed in hospital
• Smaller quantities of opioids supplied on discharge
• Fewer days in hospital
• Fewer patients taking opioids three months post-operation

Patients in the intervention group also had improved physical function and improved overall body pain intensity.

Why pharmacists should manage pre-operative opioid use

As a result of the impressive results from the OpioidHALT study Dr Jonathan Penm has now received funding of $1.5 million to run the definitive trial (OpioidHALT II). Recruitment started two months ago.

Recordings of the consultations showed that many patients were keen to discontinue opioid use but needed help with the process. “We’ve got patients who are crying [out] to have pharmacists to be more involved in their care …. and that’s something that a lot of pharmacists can do”, says Dr Penm. He adds that the whole multidisciplinary research team says “This is a really good intervention, we should be doing this, pharmacists should be leading it”

About Dr Shania Liu and Dr Jonathan Penm

Dr Shania Liu  BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FSHP, FHEA completed her PhD at the University of Sydney looking at a pharmacist-led opioid tapering program for patients undergoing total hip and knee arthroplasty. Currently, she is a post-doctoral research fellow working at the University of Alberta in Canada where she is leading two large randomised trials looking at pharmacist-partnered management of chronic conditions such as cardiovascular disease. She also  continues to be involved in the pharmacist-led opioid tapering work looking at the impacts of opioid tapering before hip and knee replacement surgery.

At the 2024 FIP Congress Dr Liu was awarded the International Pharmaceutical Federation Early Career in Pharmaceutical Practice Recognition Award. The purpose of the award is to recognise an outstanding early career pharmacist who has made important contributions to their field of practice at a national level, and who is emerging internationally.

Dr Jonathan Penm BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FFIP, FSHP, FPS, FHEA, FANZCAP (PainMgmt, Research) is a senior lecturer at the University of Sydney School of Pharmacy in Australia. He is involved in both teaching and research and is also affiliated with the Prince of Wales Hospital, where he is involved in research with the pain team. His area of interest is evaluating hospital pharmacy services to reduce patient harm and the need for hospital care.  He currently runs several randomised controlled trials and is the Principal Investigator for OpioidHALT II.

Read and watch the full series on our website or on YouTube.

Some 575 patients were screened for inclusion in the OpioidHALT study and 442 were excluded because of low opioid use. “That is the reality of clinical trials for you”, says Dr Shania Liu. “We know that approximately a quarter of patients in [this] population don’t use opioids on a regular basis”, she adds. Nevertheless, dosage tapering is still important for the many patients who are using opioids regularly.

OpioidHALT II

As a result of the impressive results from the OpioidHALT study Dr Jonathan Penm has now received funding of $1.5 million to run the definitive trial (OpioidHALT II). Recruitment started two months ago.  “What’s great about it is all of the pilot sites were so impressed by the pilot that they’ve all stayed on for this definitive trial. Other sites have also expressed interest because they’ve been so excited about it”, says Dr Penm. “We’re going to have more pharmacists, a lot more patients – and [it] will be primarily powered to look at those pain and quality of life outcomes”, he explains.

Pharmacists often improve medication regimens but rarely find out how much of an impact the changes have on patients’ lives. One of the useful and important findings in the OpioidHALT study was that the early benefits of reduced opioid use were sustained for three months. “It just shows you the value that pharmacists can provide to their patients – that when we improve their medicines we could be improving it for much, much longer than you realise and having much, much stronger impact”, says Dr Penm.

All the opioid-tapering consultations were recorded and patients’ reactions made a profound impact on Dr Penm.

“Many of them were just so grateful to have someone listen to them,  to validate what they’ve been going through with their pain and to support them through the opioids. In fact, most of them said, “I’ve never had any benefit from these but I just don’t know how to get off them – and I really would love some help”,  so I think we’ve got patients who are crying [out] to have pharmacists to be more involved in their care, to be more present, to listen to them, to validate what they’re going through – and that’s something that a lot of pharmacists can do”, he says.

In summary Dr Penm says:

“Any work of this calibre is extremely difficult to do with one person and we have a very large team. One of the unique aspects is how multidisciplinary it was – we have pharmacists, we have nurses, we have GPs, we have anaesthetists, we have physiotherapists, we have orthopaedic surgeons – and we know how rare it is to get all these people together in one spot and for all of them to say, “This is a really good intervention, we should be doing this, pharmacists should be leading it”. It’s just beautiful to hear. You don’t always hear that the pharmacist is the most obvious choice but in this case they are. They’re happy, they’re competent, they’re capable – and everyone else doesn’t want to do this because it is not their area of expertise. Well, with pharmacy we’re very comfortable because we know this, we know opioids, we see tapering, we know how to taper, we know what to expect”.

About Dr Shania Liu and Dr Jonathan Penm

Dr Shania Liu  BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FSHP, FHEA completed her PhD at the University of Sydney looking at a pharmacist-led opioid tapering program for patients undergoing total hip and knee arthroplasty. Currently, she is a post-doctoral research fellow working at the University of Alberta in Canada where she is leading two large randomised trials looking at pharmacist-partnered management of chronic conditions such as cardiovascular disease. She also  continues to be involved in the pharmacist-led opioid tapering work looking at the impacts of opioid tapering before hip and knee replacement surgery.

Dr Jonathan Penm BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FFIP, FSHP, FPS, FHEA, FANZCAP (PainMgmt, Research) is a senior lecturer at the University of Sydney School of Pharmacy in Australia. He is involved in both teaching and research and is also affiliated with the Prince of Wales Hospital, where he is involved in research with the pain team. His area of interest is evaluating hospital pharmacy services to reduce patient harm and the need for hospital care.  He currently runs several randomised controlled trials and is the Principal Investigator for OpioidHALT II.

Read and watch the full series on our website or on YouTube.

The initial consultations in the OpioidHALT study – when the opioid tapering plans were developed took about one hour. Follow-up appointments started one week after each dose reduction to check on progress and safety; these were typically shorter, explains Dr Shania Liu. Opioid withdrawal symptoms were one obvious concern. Dr Liu emphasises that the tapering rate was very gradual to minimise the risks of opioid withdrawal and patients were educated about what to look out for and how to overcome withdrawal symptoms. “If necessary the patient was put back on a higher opioid dose to ….. ensure that patient safety came first”, she says.  In fact, all adverse events were recorded during the study.

OpioidHALT findings

OpioidHALT was a pilot study designed to determine whether the intervention delivered by pharmacists led to successful tapering of opioid doses, explains Dr Jonathan Penm. “We also found that currently GPs or primary care physicians are generally responsible for opioid tapering, but that’s not their happy place – they were not comfortable, they did not want to spend their time on that”, he says.  However, pharmacists were keen to undertake this work.  The results showed that in the intervention group 90% of patients tapered their opioid doses by at least 50% before surgery compared with17% in the usual care group. “As a researcher it’s very rare to see such large differences – 17% versus 90%”, says Dr Penm.

Although the pilot study was not powered to evaluate other outcomes, some of the emerging findings suggest important impacts.  Those patients whose opioid doses were tapered before surgery consumed fewer opioids in hospital and received smaller quantities of opioids at discharge.  In addition, the length of hospital stay was shorter (4 days versus 5.6 days) in the intervention group. Three months after the surgery those in the intervention group were much less likely to be taking opioids than those in the control group. They also had improved physical function and  improved overall body pain intensity. Dr Penm notes that “it’s not powered for that so we do have to be a bit cautious  – but these are very promising results”.

About Dr Shania Liu and Dr Jonathan Penm

Dr Shania Liu  BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FSHP, FHEA completed her PhD at the University of Sydney looking at a pharmacist-led opioid tapering program for patients undergoing total hip and knee arthroplasty. Currently, she is a post-doctoral research fellow working at the University of Alberta in Canada where she is leading two large randomised trials looking at pharmacist-partnered management of chronic conditions such as cardiovascular disease. She also  continues to be involved in the pharmacist-led opioid tapering work looking at the impacts of opioid tapering before hip and knee replacement surgery.

At the 2024 FIP Congress Dr Liu was awarded the International Pharmaceutical Federation Early Career in Pharmaceutical Practice Recognition Award. The purpose of the award is to recognise an outstanding early career pharmacist who has made important contributions to their field of practice at a national level, and who is emerging internationally.

Dr Jonathan Penm BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FFIP, FSHP, FPS, FHEA, FANZCAP (PainMgmt, Research) is a senior lecturer at the University of Sydney School of Pharmacy in Australia. He is involved in both teaching and research and is also affiliated with the Prince of Wales Hospital, where he is involved in research with the pain team. His area of interest is evaluating hospital pharmacy services to reduce patient harm and the need for hospital care.  He currently runs several randomised controlled trials and is the Principal Investigator for OpioidHALT II.

Read and watch the full series on our website or on YouTube.

The case for reducing opioid treatment slowly before total hip and knee replacements is compelling, according to Dr Jonathan Penm. Many patients with osteoarthritis are taking opioids but “we know opioids are not the most effective medicine for osteoarthritis, so we’ve got a cohort of people taking a medicine that doesn’t have much evidence, that’s not very effective and comes with a lot of side effects”, he explains. Reducing the opioid doses is unlikely to make pain any worse but it could reduce the risk of harms, he adds. He notes that there is little evidence for the effectiveness of opioid dose tapering.  One previous retrospective study had shown that patients who tapered their opioids before surgery might have better post-surgical outcomes. However, as the study was not randomised it was not known if there was something different about the patients who tapered their doses. “They might just be patients who would naturally taper who weren’t as sick and so they have better outcomes – and so we just didn’t know if these harms were reversible”, he says.

OpioidHALT – objectives and methods

The objective of OpioidHALT study was to examine the feasibility and effectiveness of a pharmacist-led intervention to taper opioid dosage before hip and knee replacement surgery, compared with usual care.  The intervention was delivered via a video or telephone consultation. “Pharmacists and patients met ‘one-on-one’ over a Zoom meeting or over a telephone call and discussed their pain management and opioid use before surgery – approximately three months before their joint replacement surgery – with the aim to gradually taper their opioid dose until the day of their surgery”, explains Dr Shania Liu.

For this pilot study a single pharmacist based in the community conducted all the consultations. The pharmacist was trained using freely available, online resources. “We recently published a training package summarising these resources so any pharmacist can access them”, says Dr Liu. The pharmacist worked with each patient to  develop an opioid tapering plan that was evaluated for safety by a pain specialist. In addition, the GP was kept in the loop at all stages. Dr Liu emphasises the patient-centred nature of the consultations. “Patients could lead the level of opioid tapering that they wished. The opioid tapering rate, however, was guided by national guidelines on opioid tapering rates. So, this was, on average, 10 to 25% of the patient’s baseline opioid dose tapered per month – so quite gradual – and we did monitor for safety”, she says. Furthermore, patients were offered simple analgesics and non-pharmacological approaches to ensure that pain was managed whilst the opioid doses were being tapered.

About Dr Shania Liu and Dr Jonathan Penm

Dr Shania Liu  BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FSHP, FHEA completed her PhD at the University of Sydney looking at a pharmacist-led opioid tapering program for patients undergoing total hip and knee arthroplasty. Currently, she is a post-doctoral research fellow working at the University of Alberta in Canada where she is leading two large randomised trials looking at pharmacist-partnered management of chronic conditions such as cardiovascular disease. She also  continues to be involved in the pharmacist-led opioid tapering work looking at the impacts of opioid tapering before hip and knee replacement surgery.

At the 2024 FIP Congress Dr Liu was awarded the International Pharmaceutical Federation Early Career in Pharmaceutical Practice Recognition Award. The purpose of the award is to recognise an outstanding early career pharmacist who has made important contributions to their field of practice at a national level, and who is emerging internationally.

Dr Jonathan Penm BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FFIP, FSHP, FPS, FHEA, FANZCAP (PainMgmt, Research) is a senior lecturer at the University of Sydney School of Pharmacy in Australia. He is involved in both teaching and research and is also affiliated with the Prince of Wales Hospital, where he is involved in research with the pain team. His area of interest is evaluating hospital pharmacy services to reduce patient harm and the need for hospital care.  He currently runs several randomised controlled trials and is the Principal Investigator for OpioidHALT II.

Read and watch the full series on our website or on YouTube.

Patients who undergo total hip (THA) and total knee replacement surgery (TKA) suffer from end stage osteoarthritis with chronic pain. “We know from existing research that opioids are often no better than simple analgesics like paracetamol or acetaminophen or anti-inflammatory pain medicines for osteoarthritis-related pain – so these opioids are not providing any additional benefit and yet they carry the risk of additional side effects such as drowsiness and the risk of falls”, explains Dr Liu. Moreover, opioid use before surgery is linked to worse outcomes including slower recovery and persistent opioid use three months after surgery, she adds.

The OpioidHALT trial (Feasibility of responsible pre-operative opioid use for Hip and knee ArthropLasTy (OpioidHALT) pilot study) was designed to examine the feasibility and acceptability of an intervention to reduce opioid use before elective THA or TKA compared to usual practice. “Total hip and knee replacement surgeries are among the most common elective surgical procedures performed around the world with over 1 million of these procedures performed in the USA alone in 2021.  As we know, the population as a whole is aging so these procedures are expected to at least double in volume over the next decade”, explains Dr Liu

About Dr Shania Liu and Dr Jonathan Penm

Dr Shania Liu  BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FSHP, FHEA completed her PhD at the University of Sydney looking at a pharmacist-led opioid tapering program for patients undergoing total hip and knee arthroplasty. Currently, she is a post-doctoral research fellow working at the University of Alberta in Canada where she is leading two large randomised trials looking at pharmacist-partnered management of chronic conditions such as cardiovascular disease. She also  continues to be involved in the pharmacist-led opioid tapering work looking at the impacts of opioid tapering before hip and knee replacement surgery.

At the 2024 FIP Congress Dr Liu was awarded the International Pharmaceutical Federation Early Career in Pharmaceutical Practice Recognition Award. The purpose of the award is to recognise an outstanding early career pharmacist who has made important contributions to their field of practice at a national level, and who is emerging internationally.

Dr Jonathan Penm BPharm (Hons), GradCertEdStud (Higher Ed), PhD, FFIP, FSHP, FPS, FHEA, FANZCAP (PainMgmt, Research) is a senior lecturer at the University of Sydney School of Pharmacy in Australia. He is involved in both teaching and research and is also affiliated with the Prince of Wales Hospital, where he is involved in research with the pain team. His area of interest is evaluating hospital pharmacy services to reduce patient harm and the need for hospital care.  He currently runs several randomised controlled trials and is the Principal Investigator for OpioidHALT II.

Read and watch the full series on our website or on YouTube.

The study, published in JRSM Open, analysed data from over 1,000 people in England and Wales who logged their symptoms on an app between November 2020 and March 2022.

Pain, including headache, joint pain and stomach pain, was the most common symptom, reported by 26.5% of participants.

The other most common symptoms were neuropsychological issues such as anxiety and depression (18.4%), fatigue (14.3%), and dyspnoea (shortness of breath) (7.4%). The analysis found that the intensity of symptoms, particularly pain, increased by 3.3% on average each month since initial registration.

The study also examined the impact of demographic factors on the severity of symptoms, revealing significant disparities among different groups. Older individuals were found to experience much higher symptom intensity, with those aged 68-77 reporting 32.8% more severe symptoms, and those aged 78-87 experiencing an 86% increase in symptom intensity compared to the 18-27 age group.

Gender differences were also pronounced, with women reporting 9.2% more intense symptoms, including pain, than men. Ethnicity further influenced symptom severity, as non-white individuals with long Covid reported 23.5% more intense symptoms, including pain, compared to white individuals.

The study also explored the relationship between education levels and symptom severity. Individuals with higher education qualifications (NVQ level 3, 4, and 5 – equivalent to A-levels or higher education) experienced significantly less severe symptoms, including pain, with reductions of 27.7%, 62.8%, and 44.7% for NVQ levels 3, 4 and 5 respectively, compared to those with lower education levels (NVQ level 1-2 – equivalent to GCSEs).

Socioeconomic status, as measured by the Index of Multiple Deprivation (IMD), also influenced symptom intensity. Participants from less deprived areas reported less intense symptoms than those from the most deprived areas. However, the number of symptoms did not significantly vary with socioeconomic status, suggesting that while deprivation may exacerbate symptom intensity, it does not necessarily lead to a broader range of symptoms.

Lead author Dr David Sunkersing (UCL Institute of Health Informatics) said: “Our study highlights pain as a predominant self-reported symptom in long Covid, but it also shows how demographic factors appear to play a significant role in symptom severity.

“With ongoing occurrences of Covid-19 (e.g., LB.1, or D-FLiRT variants), the potential for more long Covid cases remains a pressing concern. Our findings can help shape targeted interventions and support strategies for those most at risk.”

In the paper, the researchers called for sustained support for long Covid clinics and the development of treatment strategies that prioritise pain management, alongside other prevalent symptoms like neuropsychological issues and fatigue.

Given the significant impact of demographic factors on symptom severity, the study underscored the need for healthcare policies that addressed these disparities, ensuring equitable care for all individuals affected by long Covid, the researchers said.

Study limitations included a lack of information on other health conditions participants may have had and a lack of information about health history. The researchers cautioned that the study may have excluded individuals with very severe Covid and those facing technological or socioeconomic barriers in accessing a smartphone app.

The study was led by the UCL Institute of Health Informatics and the Department of Primary Care and Population Health at UCL in collaboration with the software developer, Living With Ltd.

Companies like Oxycontin manufacturer Purdue Pharma have claimed that fewer than 1% of opioid prescriptions result in problems for patients.  This new review makes clear that such claims greatly understate the risk of opioid misuse and addiction.

The researchers divided the 148 studies into four general categories, depending on how the studies defined problematic opioid use:

1. dependence and opioid use disorder: 43 studies that identified problematic opioid use through diagnostic codes (formal diagnoses using precise definitions);
2. signs and symptoms of dependence and opioid use disorder:  44 studies that looked for behaviours indicating dependence and opioid use disorder, such as craving, tolerance, or withdrawal, without use of specific diagnostic codes;
3. aberrant behaviour: 76 studies that looked for inappropriate or concerning behaviour, such as seeking early refills, repeated dose escalations, or frequently lost prescriptions; and
4. at risk of dependence and opioid use disorder: 8 studies that looked for characteristics that might increase the risk of developing opioid dependence or opioid use disorder in the future; however, the characteristics do not fall within previous categories of aberrant behaviour or dependence and opioid use disorder.

Some studies reported multiple results within the same participants using different measurement criteria, so the sum of the number of studies in each category equals more than 148.  The prevalence (frequency) of problematic opioid use for each category was:

1. Dependence and opioid use disorder:  9.3%, or nearly 1 in 10 patients.
2. Signs and symptoms of dependence and opioid use disorder: 29.6%, nearly 1 in 3 patients.
3. Aberrant behaviour:  22%, more than 1 in 5 patients.
4. At risk of dependence and opioid use disorder: 12.4%, nearly 1 in 8 patients.

Lead author Kyla Thomas, Professor of Public Health Medicine at the University of Bristol, explains, “Clinicians and policy makers need a more accurate estimate of the prevalence of problematic opioid use in pain patients so that they can gauge the true extent of the problem, change prescribing guidance if necessary, and develop and implement effective interventions to manage the problem.  Knowing the size of the problem is a necessary step to managing it.”

The studies in this review were predominantly from North American research and high-income countries. One hundred and six of the 148 studies were conducted between 2010 and 2021; the oldest study was from 1985.  Study size ranged from 15 to 2,304,181 patients. Due to the high heterogeneity of the studies, these findings should be interpreted with caution.

“We sought to identify individuals who are more likely to benefit from aspirin to facilitate more personalized prevention strategies,” said co-senior author Andrew Chan, MD, MPH, Director of Epidemiology for the Mass General Cancer Center and gastroenterology Director of the Center for Young Adult Colorectal Cancer at Massachusetts General Hospital (MGH). Colorectal cancer is the second-leading cause of cancer death in the United States, according to the National Cancer Institute.

The U.S. Preventive Services Task Force previously recommended daily low-dose aspirin to prevent cardiovascular events and colorectal cancer in all adults ages 50 to 59 (the highest risk age group for colorectal cancer). In 2016, they withdrew the recommendation in part due to concerns about aspirin increasing the risk of gastrointestinal bleeding.

For the study, researchers analyzed the health data from 107,655 participants from the Nurses’ Health Study and Health Professionals Follow-Up Study. They compared the colorectal cancer rates in those who took aspirin regularly with those who did not take aspirin regularly. Regular aspirin use was defined as either two or more standard dose (325 mg) tablets per week or daily low-dose (81 mg) aspirin.

Study participants were followed starting from an average age of 49.4 years. Those who regularly took aspirin had a colorectal cancer 10-year cumulative incidence of 1.98 percent, compared to 2.95 percent among those who did not take aspirin.

The benefit of aspirin was largest among those with the unhealthiest lifestyles. Those with the lowest healthy lifestyle scores (unhealthiest) had a 3.4 percent chance of getting colorectal cancer if they did not take regular aspirin and a 2.12 percent chance of getting colorectal cancer if they took aspirin regularly. By contrast, in those with the highest healthy lifestyle scores (healthiest), the colorectal cancer rates were 1.5 percent in regular aspirin-taking group and 1.6% in the non-regular aspirin group. This means that in the least healthy group, treating 78 patients with aspirin would prevent one case of colorectal cancer over a 10-year period, while it would take treating 909 patients to prevent one case for the healthiest group. Lifestyle scores were calculated based on body mass index, frequency of cigarette and alcohol use, physical activity, and adherence to a high-quality diet.

“Our results show that aspirin can proportionally lower the markedly elevated risk in those with multiple risk factors for colorectal cancer,” said Daniel Sikavi, MD, lead author of the paper and a gastroenterologist at MGH. “In contrast, those with a healthier lifestyle have a lower baseline risk of colorectal cancer, and, therefore, their benefit from aspirin was still evident, albeit less pronounced.”

One outcome of the study could be that “healthcare providers might more strongly consider recommending aspirin to patients who have less healthy lifestyles,” said co-senior author Long H. Nguyen, MD, MS, a physician investigator in the Clinical and Translational Epidemiology Unit and Division of Gastroenterology at MGH and a Chen Institute Department of Medicine Transformative Scholar at MGH.

While the study included those who took regular standard-dose (325-mg) aspirin two times a week in the regular-aspirin using category, Sikavi noted that “based on prior studies, the best evidence supports daily low-dose (81-mg) aspirin for prevention.”

Previous studies have found evidence to suggest aspirin can reduce the production of pro-inflammatory proteins, known as prostaglandins, that can promote the development of cancer. Aspirin may also block signaling pathways that cause cells to grow out of control, influence the immune response against cancer cells, and block the development of blood vessels that supply nutrients to cancer cells. “Aspirin likely prevents colorectal cancer through multiple mechanisms,” Chan said.

The study did not assess potential side effects of daily aspirin use, such as bleeding. In addition, while the study tried to control for a wide range of risk factors for colorectal cancer, in comparing non-aspirin and aspirin-taking groups with the same level of risk factors, because this was an observational study, it is possible there may have been additional factors that influenced the findings.

Authorship: In addition to Sikavi, Chan, and Nguyen, Mass General Brigham authors include Wenjie Ma (MGH), David A. Drew (MGH), Shuji Ogino (BWH), Edward L. Giovannucci (BWH), and Mingyang Song (MGH). Additional authors include Kai Wang and Yin Cao.

Paper cited: Sikavi, D et al. “Aspirin Use and Incidence of Colorectal Cancer According to Lifestyle Risk” JAMA Oncology DOI: 10.1001/jamaoncol.2024.2503

NSAIDs continue to be a source of avoidable harm and healthcare costs, and more needs to be done to address this, especially in high risk groups, say the researchers.

NSAIDs are used for pain and inflammation and are one of the most widely prescribed groups of medicines in the world, But they are known to increase the risk of gastrointestinal bleeding, heart attacks, stroke, and kidney damage.

Yet despite a range of initiatives to reduce their use, NSAID prescribing is still common in people at high risk of harm due to older age, previous peptic ulcer, heart failure, chronic kidney disease, or who are taking other medications that can increase bleeding risk.

To help inform policy in this area, the researchers set out to estimate levels of patient harm and the costs of NSAID prescribing to high risk groups in the NHS in England over a 10 year period.

The researchers drew on previously published research on prescribing safety in England, which provided a baseline number of people affected by ‘hazardous prescribing events’ in April 2020, based on data from the national roll-out of PINCER (pharmacist-led information technology intervention for medication errors) and prevalence data from 1060 general practices (10,906,453 patients in total).

They identified rates of hazardous prescribing events for oral NSAIDs in five high risk groups: adults aged 65 and over with no gastroprotection; people with a previous peptic ulcer with no gastroprotection; people who concurrently took blood thinning drugs (anticoagulants); people with heart failure; and those with chronic kidney disease.

They then used economic models to estimate the harm associated with each hazardous prescribing event at the patient level, expressed as quality adjusted life years (QALYs) lost – a measure of years lived in good health – and the cost to the NHS in England of managing that harm.

The results show that average QALYs per person (where 1.0 is equivalent to perfect health and 0 is equivalent to being dead) were between 0.01 lower with previous peptic ulcer, to 0.11 lower with chronic kidney disease.

Average costs increased from a non-statistically significant £14 in heart failure to a statistically significant £1,097 in people also taking anticoagulants.

Rates of hazardous prescribing events per 1,000 patients ranged from 0.11 in people with a previous peptic ulcer, to 1.70 in older adults.

Nationally, the most common hazardous prescribing event (older adults without gastroprotection) results in 1,929 QALYs lost, costing £2.46 million, while the greatest impact is in people also taking anticoagulants, with 2,143 QALYs lost, costing £25.41 million.

Over 10 years, the five NSAID related hazardous prescribing events led to a total loss of 6,335 QALYs at an estimated cost of £31.43 million to the NHS in England.

Shorter durations of exposure were associated with lower risk of harms, but at least half of the observed harms occurred in the first 1.5 years of treatment.

These are observational findings, and the researchers point to several limitations around assumed dose, length of exposure, and accounting for all harms, which may have affected their estimates. And the results may not apply to other non-UK settings, they note.

However, they say the types, severity, and probability of NSAID-related harm are likely to be transferable, and further analyses to test the strength of the main findings yielded similar results, suggesting that they withstand scrutiny.

As such, they conclude: “NSAIDs continue to be a source of avoidable harm and healthcare costs, despite a range of initiatives to reduce their use, especially in populations at high risk .. therefore, a concerted effort should be made to continue to include NSAIDs in patient safety and deprescribing initiatives.”

The findings, published in the Journal of Pain Research, reveal that some women not only experience cramps when no egg is released, but that cramps can be more severe and last longer during these anovulatory cycles.

“I was surprised to see significant cramps in menstrual cycles with or without ovulation, which challenges current thinking” said co-author, Dr. Paul Yong, associate professor of obstetrics and gynecology at UBC and Canada Research Chair in Endometriosis and Pelvic Pain.

Menstrual cramps are very common, but not always well-treated by currently recommended ibuprofen therapy and may cause teen and young adult women to miss education or work.

It has long been believed that menstrual cramps are triggered by falling progesterone levels at the end of ovulatory cycles, which prompts the release of hormone-like substances, prostaglandins, that cause uterine muscle contractions.

“Since 1938, when a small research study found no cramps in anovulatory studies, no one has questioned the belief that cramps only occur in ovulatory cycles,” said co-author Dr. Sewon Bann, internist and endocrinology fellow at UBC.

For the study, the researchers monitored 75 women aged 19-35 through a single menstrual cycle. The women recorded their experiences with cramp presence and intensity in a daily diary.

“We compared cramps in the 35 cycles without ovulation with 40 cycles that were normally ovulatory in this study. We found cramps were more painful, lasted longer and had a higher Cramp Score in anovulatory cycles” said first author Gurleen Mann, a UBC medical student. Mann reports that cycle lengths were the same; fewer than one of 10 cycles in each ovulation-related group lasted longer than 35 days.

The researchers also looked at several past studies of cramps that tracked ovulation. “In a meta-analysis of the four eligible studies, all found cramps in both ovulatory and anovulatory cycles. However, in support of the current understanding, cramps were twice as likely to occur in ovulatory cycles,” said Dr. Sonia Shirin, a researcher working for UBC’s Centre for Menstrual Cycle and Ovulation Research (CeMCOR).

This single-cycle study was funded by a contract with Health Canada to collect urine to measure environmental contaminants. Recruitment took place during the early days of the SARS-CoV-2 pandemic.

“It is likely because of the multiple stresses during this difficult time that almost a third of all participants’ cycles were anovulatory,” speculated senior author Dr. Jerilynn C. Prior, a professor of endocrinology at UBC and scientific director at CeMCOR.

The researchers say this new information about menstrual cramps and ovulation has several important implications:

• We can no longer assume a cycle is ovulatory just because it has menstrual cramps
• It is unlikely to be the decreasing levels of progesterone before flow, as is currently understood, that trigger menstrual cramps
• New research is necessary to understand what other changes trigger cramps
• Learning more about why cramps occur will help with treatment of cramps that are severe or cause absence from school or work.