Category: Medicine

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Tramadol Linked to Increased Hip Fracture Risk in Elderly

Older patients treated with the pain medication tramadol show significant increases in the risk of hip fracture compared with those using codeine or commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), new research shows.

“Considering the significant impact of hip fracture on morbidity, mortality, and healthcare cost, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” first author Jie Wei, PhD, an associate professor of epidemiology at Xiangya Hospital, Central South University, China, told Medscape Medical News.

In commenting on the research, Shailendra Singh, MD, noted that the “article clearly reinforces [prior] knowledge…that opiates are associated with an increased risk of falls and fractures.”

The American Geriatric Society BEERS criteria for inappropriate drugs for the elderly, for instance, lists tramadol and opiates as drugs to avoid in patients with increased risk of falls and fractures, added Singh, who is rheumatology medical director of the White River Medical Center in Batesville, Arkansas, and was not involved with the current study.

Increased Risk of Hip Fracture With Tramadol Even Compared With Codeine  

The new study, published this month in the Journal of Bone and Mineral Research, involved data on 146,956 patients in the United Kingdom who were age 50 years and older and enrolled in The Health Improvement Network (THIN).

The patients had initiated treatment with tramadol between 2000 and 2017 for noncancer-related pain, and had no history of hip fracture, cancer, or opioid use disorder.

In the propensity-matching analysis, those initiating tramadol were matched 1:1 with well-balanced characteristics to patients identified as initiating codeine during the same period (146,956 in each group).

Equal-numbered groups were also matched between tramadol and naproxen (115,109 in each group) or ibuprofen (107,438 per group), both NSAIDs, or celecoxib (43,130 per group) or etoricoxib (27,689 per group), which are both cyclooxygenase‐2 inhibitors.

Participants in the matched groups had a mean age of 65 and 56.9% were women.

For the primary outcome of the incidence of hip fracture over 1 year, the risk was higher for tramadol compared with codeine (hazard ratio [HR], 1.28), with 518 cases of hip fracture (3.7 per 1000 person-years) in the tramadol cohort and 401 (2.9 per 1000 person-years) in the codeine cohort.

Likewise, the risk was higher with tramadol compared with naproxen (HR, 1.69), ibuprofen (HR, 1.65), celecoxib (HR, 1.85), and etoricoxib (HR, 1.96).

A sensitivity analysis restricted to individuals aged 60 or older showed no major differences in the associations for all of the drug groups.

“The sensitivity analyses had similar results, indicating that the observed associations were robust and raising a concern on the potential risk of hip fracture among initiators of tramadol use,” the authors say.

The increased risk compared with the initiation of codeine is particularly notable, as codeine is regarded as a weak opioid and often used in a similar context as tramadol, Wei noted.

“The risk of incident hip fracture among tramadol initiators was not only higher than that among NSAIDs initiators, but also higher than that among codeine initiators, suggesting that the confounding by indication may not substantially account for an increased risk of hip fracture for tramadol,” she observed.

She added that “this was further supported by the evidence that risk factor profiles between initial prescription of tramadol and that of codeine were similar even before propensity-matching, except a few (for instance BMI was higher among tramadol than codeine prescriptions).”

“Nevertheless, as in all observational studies, we can’t rule out the impact of potential residual confounders when comparing the risk of hip fracture between initial prescription of tramadol and other pain-relief medications,” Wei stressed.

Tramadol Seen as Beneficial NSAID Alternative for Pain

Tramadol is seen as a valuable analgesic alternative to NSAIDs, with perceived lower cardiovascular and gastrointestinal effects while providing a reduced risk of addiction and respiratory depression compared with traditional opioids, the authors note.

Guidelines of professional organizations recommend tramadol for pain under various conditions, including the most recent guidelines of the American College of Rheumatology (ACR), which conditionally recommend tramadol for the treatment of knee or hip osteoarthritis, “including when patients may have contraindications to NSAIDs, find other therapies ineffective, or have no available surgical options.”

Use of the drug has been on the rise worldwide in recent decades, with one survey showing a 22.8% increase in tramadol prescriptions in the US from 2012 to 2015.

The authors note that important limitations of the study include the fact that the THIN database does not include measures on two potentially important confounders — bone density and frailty.

Singh said it’s unknown whether propensity score matching can adjust for important factors, such as the severity of disease: “(For instance), people with severe osteoporosis are at a higher risk of fracture, compared to moderate…the lower the T-score, the higher the risk of fracture.”

Link Between Increased Risk of Falls and Tramadol?
Don’t Prescribe It First-Line

As reported by Medscape Medical News, Wei and her colleagues showed an association between tramadol use and a higher risk of all-cause mortality among patients in the THIN network in a study published last year.

The specific mechanisms linking tramadol use to an increased risk of mortality remain unclear, however.

And that study, which — as opposed to the current one — was limited to patients with osteoarthritis pain, showed the increased mortality risk did not extend to those treated with codeine.

Although the mechanisms that may explain the increased risk of fracture are not known, Wei and colleagues note previous research suggesting an effect of tramadol in activating mu-opioid receptors while suppressing central serotonin and norepinephrine reuptake, which can be linked to the risk of seizures, dizziness, and/or delirium — all of which could increase the risk of fall.

“In fact, several studies have reported that tramadol use was indeed associated with a higher risk of fall, which is a critical risk factor for fracture,” they note.

“All these studies appear to suggest that relation of tramadol to the risk of hip fracture may be, at least partly, through its effect on fall,” they surmise.

“In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice.”

Singh agrees. While underscoring that further studies are needed to determine the mechanism of action in the increased hip fracture risk, he concluded that “opiates of any kind, including tramadol, should not be used as a first line drug for pain management in any setting.”

Source : Medscape

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Handheld 3D Printer Delivers Skin-Precursor Sheets Directly to Full-Thickness Burns

A new handheld 3D printer can be used to deliver skin-precursor sheets directly to wound beds and improve healing in full-thickness burns, according to a preclinical study in a porcine model.

“The ability to consistently deliver (human) cells in a matrix and onto practically relevant wound surfaces, i.e., of arbitrary size and topology, has been a significant limitation that we believe has been overcome with our handheld instrument,” Dr. Alex Guenther of the University of Toronto, in Canada, told Reuters Health by email.

Large burn areas often leave insufficient healthy skin to use as autologous skin grafts. Acellular biodegradable scaffolds have been used as alternatives, and different cellular approaches using patient-derived autologous or donor-derived allogeneic cells are under development.

Dr. Guenther and colleagues developed a handheld 3D bioprinter designed to deliver a fibrinogen-based bioink containing mesenchymal stromal cells directly onto burn-wound surfaces of arbitrary size, shape and topography.

A burn area of 2,000 cm2 (similar to an average burn area of the human posterior trunk or about 10% of total body surface) would require about 40 mL of biomaterial with 40 million cells in total, with a deposition time of 70 minutes, the researchers report in Biofabrication.

The time required to cover a full-thickness burn wound size of 5×5 cm took an average of 0.89 min, using 480 uL of biomaterials with a total of 480,000 cells.

The researchers treated full-thickness burn wounds on four porcine models using the handheld instrument and found that the wounds were uniformly covered with the deposited material immediately after delivery.

After 28 days, the treated wounds showed superior healing profiles with a reduction in inflammation, scarring, and contraction, compared with untreated burns and burns treated with acellular materials.

Histologically, treated wounds showed epidermal cell repopulation in normal ranges, whereas burn controls and acellular treatments showed regions with poor cell repopulation in addition to localized areas with hyperplasia or hypoplasia.

“Cell delivery of bioprinting should in many clinical cases probably not be done with a printer that is scaled to patient dimensions,” Dr. Guenther said. “That would make for a very bulky instrument. In contrast, we believe the demonstrated handheld device is advantageous. Also, because its form is similar to another handheld instrument routinely used by burn surgeons for many decades: a dermatome.”

Co-author Dr. Marc G. Jeschke of Sunnybrook Health Sciences Centre, also in Toronto, told Reuters Health by email, “This could change the way we practice for burn patients and patients with large wounds as we could restore a patients skin with no scar, no pain as we avoid donor sites and a significantly shortened hospital stay from months to weeks.”

“We have not shown that printing can restore autologous skin of a patient yet,” he said. “The issue at this time is showing efficacy, but this is being studied.”

Source : Medscape

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Bariatric Surgery Tied to Lowered Risk of Colorectal Cancer

Bariatric surgery may lower patients’ risk of developing colorectal cancer, a research review suggests.

Obesity has long been linked to increased risk of colorectal tumors and other types of cancer, as well as a greater risk for chronic illnesses like diabetes and heart disease. Losing weight is thought to reduce these risks.

“Our findings further support . . . that these surgeries do in fact have an overall protective effect among the obese population in terms of reducing colorectal cancer,” said Dr. Sulaiman Almazeedi of Jaber Al-Ahmed Hospital in Kuwait, who led the study.

The researchers examined data from seven previous studies that followed more than 1.2 million patients for about seven years, on average. Colorectal cancer was rare, developing in just 638 people during the study.

Compared to obese individuals who didn’t get bariatric surgery, those who did were 35% less likely to develop colorectal cancer, the researchers report in the British Journal of Surgery.

“Obesity is one of the most preventable causes of early death and it, as an epidemic, should not be taken lightly,” Almazeedi told Reuters Health by email. “Although lifestyle modifications and medical therapy have long been the cornerstone of this problem, bariatric surgery is proving day by day to be of vital importance in this battle.”

The studies in the analysis used a variety of methods and none was designed to prove bariatric surgery directly affects colorectal cancer risk.

Researchers also lacked information on preoperative body mass index, postoperative weight loss, and type of bariatric surgery.

“The primary explanation for reduction in cancer including colorectal cancer following bariatric surgery is the extent of weight loss which occurs,” said Dr. Bruce Wolfe, a researcher at Oregon Health and Science University in Portland, who wasn’t involved in the study.

Earlier research suggests obese people need to lose 20% of their body weight to get the best outcome in terms of reducing the risk of cancer, Wolfe said by email. Bariatric surgery is the best way to accomplish this, he said.

When people lose weight after bariatric surgery, many changes happen that impact cancer risk, said Dr. Daniel Schauer of the University of Cincinnati College of Medicine, in Ohio.

“Perhaps most importantly for colorectal cancer risk, the body has less inflammation and many of the (tumor) growth factors associated with obesity are decreased,” Schauer, who also wasn’t involved in the study, said by email. “These are strongly related to the amount of weight loss.”

Data from this study were presented at the XXIV World Congress of the International Federation for the Surgery of Obesity and Metabolic Disorders, Madrid, Spain, September 2019.

Source : Medscape

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Biopsy Kidneys From Live Donors to Predict Transplant Success

Subclinical structural features in kidneys from living donors that can only be seen with a microscope modestly contribute to predicting the long-term success of a transplant, new research suggests.

In an analysis that involved 2293 living donor-recipient pairs, intraoperative biopsy of the renal cortex of the donated kidney was performed to identify factors that predicted future graft failure — independent of donor and recipient risk factors, including age and kidney function.

These came down to interstitial fibrosis/tubular atrophy, larger cortical nephron size (although not nephron number), and smaller medullary volume.

“We think that these subtle abnormalities in the living kidney donor may make the kidney more susceptible to fail in the future in recipients,” lead investigator Naim Issa, MD, Mayo Clinic, Rochester, Minnesota, said in a statement from his institution. The study was published online January 23 in the Journal of the American Society of Nephrology.

“These important findings may provide insights into unrecognized predictors of kidney transplant failure in recipients,” Issa added.

However, he and his colleagues stress that even if these subtle structural abnormalities are detected in a living donor kidney, the findings should not deter anyone’s decision to donate his or her kidney to a patient who needs one.

Patients who receive a live donor kidney generally have better outcomes than those who receive a deceased donor organ, largely because kidneys from living donors tend to last longer than those from deceased donors.

Aging Kidney Anatomy Study

In the United States last year, nearly 7400 living donor transplants were performed, according to the United Network for Organ Sharing; it was a record year for living organ donation in the US but still a far cry from the nearly 95,000 organs needed for patients who are still awaiting a donor kidney.

Living kidney donation has become the preferred therapeutic option for patients with end-stage renal disease. A thorough clinical evaluation with laboratory testing is required to ensure the donor has healthy kidneys.

Despite this, certain live donor clinical characteristics (particularly older age and lower glomerular filtration rate) predict an increased risk of death-censored graft failure in the recipient.  

These clinical characteristics may reflect underlying structural features in the kidney that are predictive of longevity of the graft, so the researchers set out to examine kidney structural predictors of death-censored graft failure.

The study took place in 3 transplant centers involved in the Aging Kidney Anatomy study — donor and recipient pairs at Mayo Clinic Minnesota (n = 1585), Mayo Clinic Arizona (n = 436), and Cleveland Clinic in Ohio (n = 272) — examining organs donated between May 1999 and December 2017.

“All kidney donors underwent a thorough medical evaluation prior to donation that included a prescheduled series of tests,” including a CT scan, the researchers note. And an intraoperative needle core biopsy of the renal cortex of the donated kidney was performed during transplantation.

During follow-up, 12.5% of recipients developed death-censored graft failure and 18.5% of donor recipients died.

The mean time to death-censored graft failure or last follow-up was 6.3 years, the authors note.

“Each kidney structural feature on biopsy or CT scan at the time of transplantation was evaluated as a predictor of death-censored graft failure,” they explain.

Findings Support Biopsies to ID Grafts at Higher Risk of Failure

After adjusting for both donor and recipient clinical characteristics, the structural features that appeared to affect the life span of a posttransplant kidney were the percentage of interstitial fibrosis/tubular atrophy (IF/TA) in the allograft (an IF/TA >5%); arteriolar hyalinosis as detected by the pathologist on biopsy slides; larger glomeruli and tubules; and smaller medulla at the time of donation.

These all modestly predicted for death-censored graft failure, the authors elaborate.

“[These findings] provide important insights into the factors that define the ‘intrinsic quality’ of the living kidney donor graft at the time of donation and support the use of intraoperative biopsies to identify kidney allografts that are at higher risk for failure,” they emphasize.

The investigators point out that intraoperative kidney biopsy has very low risk for harm, with any bleeding easily controlled by the surgeon.

However, they reiterate that even with the abnormalities detected on biopsy,

“Availability of a willing person with acceptable health for kidney donation will generally supersede concerns regarding graft quality.”

“And if the biopsy shows arteriolar hyalinosis, IF/TA >5% or enlarged nephrons…[transplant recipients] may benefit from non-CNI (calcineurin inhibitor)-based immunosuppression or more aggressive management of blood pressure to prevent worsening arteriolar hyalinosis or nephron enlargement,” they indicate.

However, the researchers also caution, “Further studies are needed to determine if recipient management benefits from modifications based on the living donor biopsy findings.”

Source : Medscape

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Top Risk Factor for Mental Disorders Identified

Early life adversity including neglect and physical, emotional, and sexual abuse is the single biggest risk factor for psychiatric disorders, new research suggests.

In what has been described as a seminal review, investigators at Dell Medical School in Austin, Texas, conclude that childhood maltreatment is “by far” the biggest contributing factor leading to impaired health in adults.

Dr. Charles Nemeroff, MD, PhD

Physically, early abuse is associated with reduced life expectancy due to higher risk for heart disease, stroke, obesity, diabetes, and certain forms of cancer, study co-author Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry at Dell’s Mulva Clinic for the Neurosciences, and director of its Institute for Early Life Adversity Research, told Medscape Medical News.

In terms of the psychiatric impact, “maltreatment increases the risk for depression, drug abuse, suicide, alcohol abuse, and it also worsens the course of all psychiatric disorders that have been looked at,” Nemeroff added.

The paper was published in the January issue of the American Journal of Psychiatry.

High Rates of Maltreatment an Underestimate?

Shockingly, estimates show that about one in four children will experience abuse or neglect, although this might well be an underestimate as most cases of maltreatment go unreported.

“This is especially true for certain types of childhood maltreatment (notably emotional abuse and neglect), which may never come to clinical attention but have devastating consequences on health independently of physical abuse and neglect or sexual abuse,” Nemeroff and co-author Elizabeth Lippard, PhD, write.

Pointing to a recent meta-analysis showing that 46% of patients with depression experienced childhood maltreatment, the authors also note that up to 57% of patients with bipolar disorder also report high levels of childhood abuse and/or neglect.

The research also suggests childhood maltreatment is associated with poor treatment outcomes in patients with depression, post-traumatic stress disorder (PTSD), or bipolar disorder.

These findings underscore the need for clinicians to conduct detailed evaluations of trauma history, said Nemeroff.

“It’s extremely important for clinicians to get a detailed childhood trauma history of a patient so they know what they’re dealing with. Many patients don’t volunteer information, particularly during the first visit, about whether they have had any adverse early childhood experiences,” he said.

“We need to try to understand how best to treat these patients because they don’t respond well to conventional treatments — medication or psychotherapies,” said Nemeroff.

Evolving research is examining the timing, duration, and severity of childhood maltreatment. Some studies suggest maltreatment earlier in life that continues for a longer period is associated with worse outcomes. However, the authors emphasize that exposure to maltreatment at any time during childhood significantly increases the risk for mood disorders.

The review also includes studies of the negative consequences of bullying. While there’s some evidence to indicate that cyberbullying often precipitates suicide and that this appears to occur more often with women than men, said Nemeroff, much of the data in this area is “anecdotal.”

Most Prevalent, Least Studied

With respect to subtypes of childhood maltreatment, the authors note that emotional abuse and neglect are likely the most prevalent in psychiatric populations, but are the least studied.

In part, this is because patients who experience these types of abuse are often the least likely to come to clinical attention compared with those with physical and sexual abuse, which often results in physical injury.

“In many studies, but not all, neglect has the most devastating consequences in terms of mood and anxiety disorders,” said Nemeroff. However, he added, few individuals suffer a single isolated type of abuse.

“Very often, they’re victims of mixed forms of abuse like physical and sexual abuse, and emotional abuse.”

Emerging evidence suggests childhood maltreatment may increase the risk for mood disorders and disease progression via inflammation, as indicated by measures such as C-reactive protein (CRP) and inflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6.

Anti-inflammatory medications are a promising novel therapeutic strategy in depressed patients with elevated inflammatory markers. However, this evidence is still preliminary, the authors note.

Another potential mechanism is through alterations of the hypothalamic-pituitary-adrenal axis and corticotropin-releasing factor (CRF) circuits that regulate endocrine, behavioral, immune, and autonomic responses to stress.

Genetic predisposition also likely plays a role in the pathogenesis of mood disorders following early life stress. Only 35% to 40% of individuals exposed to traumatic events will develop PTSD, said Nemeroff. “That’s probably largely determined by genetics.”

He estimated there might be a dozen or so genes, each of which provides a small degree of vulnerability to psychiatric disorders after exposure to trauma.

Intergenerational Genetic Trauma

The authors also point to novel research pertaining to the complex area of intergenerational transmission of trauma and psychopathology — a phenomenon that has been studied in Holocaust victims.

“It turns out that when an individual is traumatized, their ova, in the case of women, and sperm cells, in the case of men, can be changed by epigenetic mechanisms,” said Nemeroff. “In that way, the child that’s a product of these gametes can carry with it an effect of previous generations’ trauma.”

Research also suggests that childhood maltreatment may lead to structural and functional brain imaging changes. Some evidence has linked early abuse with lower gray matter volumes and thickness in the ventral and dorsal prefrontal cortex, including the orbitofrontal and anterior cingulate cortices, hippocampus, insula, and striatum.

Studies that are more recent also suggest an association with decreased white matter structural integrity within and between these regions.

“Different types of abuse and neglect result in different brain changes. It probably depends in part on how old the child is at time of the insult,” said Nemeroff.

Researchers are gaining ground in understanding why not all people exposed to childhood trauma develop a mood disorder. Environmental factors, as well as genes, may mediate the relationship between childhood abuse and mood disorders, the review authors note.

Studies also show that social support and secure attachments can buffer depression risk.

Nemeroff believes there are three critical areas for further research. These include determining whether brain and body changes that occur because of childhood abuse and neglect are reversible. In addition, he said, there needs to be more research into optimal treatments for this patient population and better methods of identifying those at risk of early adversity.

“It won’t be long before genome-wide scanning will become part of the electronic medical record,” said Nemeroff. “We screen for genetic diseases all the time in other areas; why wouldn’t we do it for this?”

In addition, when at-risk patients are identified, interventions could focus on the family unit, single parents, families living in poverty, and parents working two jobs, said Nemeroff.

Educating guidance counselors, teachers, and nurses, is also important, he said, but it is also critically important to educate clinicians about how to conduct proper evaluations.

Strengths, Limitations

Commenting for Medscape Medical News, David Fassler, MD, clinical professor of psychiatry, Larner College of Medicine, University of Vermont, Burlington, described the review as “comprehensive.”

The authors “demonstrate that the available research consistently supports the finding that childhood maltreatment increases the risk of mood disorders,” said Fassler.

“They also appropriately address the limitations of their review, including varying definitions of maltreatment and the use of different assessment instruments across studies,” he said.

Given the prevalence of childhood maltreatment, the review “further underscores the importance of comprehensive initiatives designed to protect young people from such traumatic and harmful experiences. Hopefully, the findings will also inform future research on the treatment and prevention of adult mood disorders,” Fassler said.

Source : Medscape

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FDA Approves Tazemetostat, First Drug for Epitheloid Sarcoma

For the first time, a drug has been approved by the US Food and Drug Administration (FDA) for the treatment of epithelioid sarcoma, a rare subtype of soft tissue sarcoma that occurs in young adults.

The drug is tazemetostat (Tazverik, Epizyme Inc), and it acts as an inhibitor of EZH2 methyltransferase. It is indicated for the treatment of metastatic or locally advanced epithelial sarcoma in cases in which complete resection is not possible.

This is the first drug with that mechanism of action, and it is the first to be indicated for epithelioid sarcoma, the agency noted.

The FDA granted an accelerated approval on the basis of response rate data from an open-label clinical trial in 62 patients. All patients received tazemetostate 800 mg twice daily. The overall response rate was 15% (9 of 62 patients), with 1.6% of patients having a complete response and 13% having a partial response. Among the nine patients who had a response, six (67%) patients had a response that lasted 6 months or longer.

The most common side effects were pain, fatigue, nausea, decreased appetite, vomiting, and constipation. Tazemetostate may increase the risk for secondary malignancies, the agency noted.

When these data were discussed at a recent meeting of the FDA’s Oncologic Drugs Advisory Committee, “the committee voted unanimously that the benefits of the drug outweighed the risks,” commented Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

“Until today, there were no treatment options specifically for patients with epithelioid sarcoma,” he added. This approval “provides a treatment option that specifically targets this disease.”

Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial. The manufacturer is now conducting a global, randomized, controlled confirmatory trial to assess the combination of tazemetostat plus doxorubicin compared with doxorubicin plus placebo as a frontline treatment for epithelial sarcoma.

Rare Tumor, Often Metastatic on Diagnosis

Epithelioid sarcoma is rare. It accounts for fewer than 1% of all sarcomas and is diagnosed in 150 to 200 people in the United States each year.

The diagnosis can be easily missed. The disease often presents as a hard lump in soft tissue, such as under the skin in the extremities or in the abdomen or groin, in young adults (aged 20–30 years) who are apparently healthy.

Surgery is usually considered if the tumor is localized in one part of the body. Chemotherapy and radiotherapy may also be given, the FDA notes. However, there is a high likelihood of local and regional spread of the disease even with treatment, and approximately 50% of patients have metastatic disease at the time of diagnosis. Metastatic disease is considered life-threatening, the agency notes.

“There are limited therapeutic options for treating patients with epithelioid sarcoma, who struggle with high rates of recurrence and toxicities associated with currently used therapies,” said Gary K. Schwartz, MD, chief of hematology and oncology at Columbia University and New York–Presbyterian Hospital, New York City. He was the lead investigator of the clinical trial of tazemetostat.

The results from that trial “support its potential to provide clinically meaningful and durable responses, and tolerability,” he said in a statement.

“For people with epithelioid sarcoma, an aggressive life-threatening cancer that affects young adults, having new treatment options can offer much needed hope,” added Denise Reinke, MS, NP, MBA, president and chief executive officer of the Sarcoma Alliance for Research Through Collaboration (SARC) and cofounder of the Sarcoma Coalition.

Source : Medscape

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Low-Dose CT Reduces Radiation Exposure Without Missing Injuries in Trauma Patients

In blunt trauma patients, low-dose whole body computed tomography (WBCT) does not seem to increase the risk of missed injury diagnoses compared with standard-dose protocols, and almost halves exposure to diagnostic radiation, a quasi-experimental study suggests.

“In suspected multiple trauma, radiological imaging…plays an integral role during initial work-up and resuscitation,” Dr. Dirk Stengel of BG Kliniken-Klinikverbund der Gesetzlichen Unfallversicherung gGmbH in Berlin told Reuters Health by email. “In industrialized countries and at designated trauma centers, an early WBCT scan from the skull to the pelvis – often coined the ‘pan-scan’ – emerged as a preferred option to screen for life-threatening injuries.”

“As many patients are rather young,” he said, “excess radiation with a liberal pan-scan policy remains an issue of debate.”

Several imaging approaches for reducing noise and radiation in CT technology are available from major manufacturers of high-end multisclice scanners, he noted. “No previous large-scale study had investigated the clinical effects – i.e., rate of missed injuries, diagnostic accuracy – of lowering the radiation dose to the currently achievable minimum.”

Dr. Stengel and colleagues recruited 565 consecutive patients admitted for suspected blunt multiple trauma from September 2014 through July 2015 for the standard-dose protocol, and 509 patients from August 2015 through August 2016 for the low-dose protocol.

As reported in JAMA Surgery, 971 patients (mean age, 52.7; 66.8% men) completed the study. One hundred and fourteen (11.7%) had multiple trauma, defined as an Injury Severity Score of 16 or greater.

A missed injury diagnosis at the point of care was defined as any injury demanding clinical awareness or therapeutic action at any time, but that was not recognized in the initial WBCT or contained in the initial (“hot”) report provided to the trauma team.

The proportion of patients with any such injury was 23.3% in the standard-dose and 21.3% in the low-dose WBCT groups (unadjusted odds ratio, 0.89). Adjustments for autocorrelation and multiple confounding variables did not alter the results.

Radiation exposure, measured by the volume CT dose index, was lowered from a median of 11.7 mGy in the standard-dose group to 5.9 mGy in the low-dose group. The median dose-length product was reduced from 1,109 mGy/cm to 735 mGy/cm.

Further, the contrast-to-noise ratio consistently favored low-dose WBCT for all investigated anatomical regions.

Dr. Stengel said, “We conclude that, if WBCT scanning is considered the diagnostic strategy of choice, it should be performed at low-dose using a modern iterative image-processing algorithm.”

With that said, based on a 2012 report from the same team (http://bit.ly/2Gi4Mob), “we stress that an initially ‘negative’ WBCT scan is not confirmative,” he added. “Certain injuries in trauma patients simply need time to demark. In the early phase of resuscitation, patients may have a centralized circulatory system, and active bleeding to the large body cavities – i.e., cranium, thorax, abdomen, retroperitoneum, pelvis – can only be detected after volume has been replaced.”

“We urge trauma teams worldwide to find the appropriate balance amongst the ideal time of scheduling patients to a WBCT scan and its capability to detect injuries,” he concluded.

Dr. Anthony Charles of the University of North Carolina at Chapel Hill, coauthor of a related editorial, noted in an email to Reuters Health that although it was a good study, he has concerns.

“In trauma, there is acuity, and the risk of missed injury is much higher than a very low potential risk of radiation-induced cancer in the future,” he said. “In addition, this study had a high baseline risk of missed injury within the regular and low-dose WBCT groups – certainly, a lot higher missed injury rate than we see in the United States.”

“If they had missed injury rates similar to the U.S., this study would have shown that low-dose WBCT resulted in a higher missed injury rate,” he said.

“The strength of any radiologic study is in the image quality and the interpretation,” he added. “Radiologists as well as trauma surgeons (who also must concur with the radiologist interpretations of any image) must be confident that low-dose WBCT can yield the same results. This will take time and practice, but more importantly, more robust studies before one can allow low-dose WBCT to go mainstream.”

Source : Medscape