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Tear Proteins May Be Biomarkers for Parkinson’s Disease
LOS ANGELES—Tears may hold diagnostic clues as to whether someone has Parkinson’s disease, according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. “We believe our research is the first to show that tears may be a reliable, inexpensive, and noninvasive biologic marker of Parkinson’s disease,” said study author Mark Floyd Lew, MD, Professor of Clinical Neurology, and Joseph P. Van Der Meulen, MD, Chair in Parkinson’s Disease Research in Honor of Robert J. Pasarow, and Vice Chair, in the Department of Neurology at the Keck School of Medicine of the University of Southern California in Los Angeles.
Nonmotor features of Parkinson’s disease occur years prior to motor dysfunction and represent a well-suited platform to investigate for a possible biomarker. Lacrimal glands are highly innervated by cholinergic neurons, and tear fluid secreted by lacrimal glands is greatly stimulated by cholinergic neurons. The production, packaging, and secretion of specific proteins into tears may be regulated by changes in nerve function to lacrimal glands. According to the researchers, analysis of any alteration in the secretion of proteins into tears may identify a reliable and noninvasive biomarker for Parkinson’s disease.
For the study, tear samples were collected from 55 patients with Parkinson’s disease of varying severity and 27 age- and gender-matched controls without Parkinson’s disease. In addition, tears were analyzed for the levels of four proteins—total alpha synuclein, CC chemokine ligand 2 (CCL-2), DJ-1 (Parkinson’s disease protein 7), and oligomeric alpha synuclein.
The researchers found differences in the levels of a total alpha-synuclein in the tears of patients with Parkinson’s disease, compared with those of controls. Additionally, levels of oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson’s disease, were also significantly different, compared with controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears, the researchers said.
Total levels of alpha-synuclein were decreased in patients with Parkinson’s disease, with an average of 423 picograms of that protein per milligram (pg/mg) compared with 704 pg/mg in healthy controls. However, levels of oligomeric alpha-synuclein were increased in patients with Parkinson’s disease, with an average of 1.45 nanograms per milligram of tear protein (ng/mg), compared with 0.27 ng/mg in controls. While detectable in tears, neither CCL-2 nor DJ-1 varied between patients with Parkinson’s disease and controls.
“Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson’s disease and those who do not in a noninvasive manner is exciting,” said Dr. Lew. “And because the Parkinson’s disease process can begin years or decades before symptoms appear, a biologic marker like this could be useful in diagnosing, or even treating, the disease earlier.”
More research needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest presymptomatic stages of the disease, said the researchers.
The study was supported by the Michael J. Fox Foundation for Parkinson’s Research and the Plotkin Foundation.
LOS ANGELES—Tears may hold diagnostic clues as to whether someone has Parkinson’s disease, according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. “We believe our research is the first to show that tears may be a reliable, inexpensive, and noninvasive biologic marker of Parkinson’s disease,” said study author Mark Floyd Lew, MD, Professor of Clinical Neurology, and Joseph P. Van Der Meulen, MD, Chair in Parkinson’s Disease Research in Honor of Robert J. Pasarow, and Vice Chair, in the Department of Neurology at the Keck School of Medicine of the University of Southern California in Los Angeles.
Nonmotor features of Parkinson’s disease occur years prior to motor dysfunction and represent a well-suited platform to investigate for a possible biomarker. Lacrimal glands are highly innervated by cholinergic neurons, and tear fluid secreted by lacrimal glands is greatly stimulated by cholinergic neurons. The production, packaging, and secretion of specific proteins into tears may be regulated by changes in nerve function to lacrimal glands. According to the researchers, analysis of any alteration in the secretion of proteins into tears may identify a reliable and noninvasive biomarker for Parkinson’s disease.
For the study, tear samples were collected from 55 patients with Parkinson’s disease of varying severity and 27 age- and gender-matched controls without Parkinson’s disease. In addition, tears were analyzed for the levels of four proteins—total alpha synuclein, CC chemokine ligand 2 (CCL-2), DJ-1 (Parkinson’s disease protein 7), and oligomeric alpha synuclein.
The researchers found differences in the levels of a total alpha-synuclein in the tears of patients with Parkinson’s disease, compared with those of controls. Additionally, levels of oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson’s disease, were also significantly different, compared with controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears, the researchers said.
Total levels of alpha-synuclein were decreased in patients with Parkinson’s disease, with an average of 423 picograms of that protein per milligram (pg/mg) compared with 704 pg/mg in healthy controls. However, levels of oligomeric alpha-synuclein were increased in patients with Parkinson’s disease, with an average of 1.45 nanograms per milligram of tear protein (ng/mg), compared with 0.27 ng/mg in controls. While detectable in tears, neither CCL-2 nor DJ-1 varied between patients with Parkinson’s disease and controls.
“Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson’s disease and those who do not in a noninvasive manner is exciting,” said Dr. Lew. “And because the Parkinson’s disease process can begin years or decades before symptoms appear, a biologic marker like this could be useful in diagnosing, or even treating, the disease earlier.”
More research needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest presymptomatic stages of the disease, said the researchers.
The study was supported by the Michael J. Fox Foundation for Parkinson’s Research and the Plotkin Foundation.
LOS ANGELES—Tears may hold diagnostic clues as to whether someone has Parkinson’s disease, according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. “We believe our research is the first to show that tears may be a reliable, inexpensive, and noninvasive biologic marker of Parkinson’s disease,” said study author Mark Floyd Lew, MD, Professor of Clinical Neurology, and Joseph P. Van Der Meulen, MD, Chair in Parkinson’s Disease Research in Honor of Robert J. Pasarow, and Vice Chair, in the Department of Neurology at the Keck School of Medicine of the University of Southern California in Los Angeles.
Nonmotor features of Parkinson’s disease occur years prior to motor dysfunction and represent a well-suited platform to investigate for a possible biomarker. Lacrimal glands are highly innervated by cholinergic neurons, and tear fluid secreted by lacrimal glands is greatly stimulated by cholinergic neurons. The production, packaging, and secretion of specific proteins into tears may be regulated by changes in nerve function to lacrimal glands. According to the researchers, analysis of any alteration in the secretion of proteins into tears may identify a reliable and noninvasive biomarker for Parkinson’s disease.
For the study, tear samples were collected from 55 patients with Parkinson’s disease of varying severity and 27 age- and gender-matched controls without Parkinson’s disease. In addition, tears were analyzed for the levels of four proteins—total alpha synuclein, CC chemokine ligand 2 (CCL-2), DJ-1 (Parkinson’s disease protein 7), and oligomeric alpha synuclein.
The researchers found differences in the levels of a total alpha-synuclein in the tears of patients with Parkinson’s disease, compared with those of controls. Additionally, levels of oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson’s disease, were also significantly different, compared with controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears, the researchers said.
Total levels of alpha-synuclein were decreased in patients with Parkinson’s disease, with an average of 423 picograms of that protein per milligram (pg/mg) compared with 704 pg/mg in healthy controls. However, levels of oligomeric alpha-synuclein were increased in patients with Parkinson’s disease, with an average of 1.45 nanograms per milligram of tear protein (ng/mg), compared with 0.27 ng/mg in controls. While detectable in tears, neither CCL-2 nor DJ-1 varied between patients with Parkinson’s disease and controls.
“Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson’s disease and those who do not in a noninvasive manner is exciting,” said Dr. Lew. “And because the Parkinson’s disease process can begin years or decades before symptoms appear, a biologic marker like this could be useful in diagnosing, or even treating, the disease earlier.”
More research needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest presymptomatic stages of the disease, said the researchers.
The study was supported by the Michael J. Fox Foundation for Parkinson’s Research and the Plotkin Foundation.
Tip for when using phenazophyridine
Tip for when using phenazophyridine
I enjoyed the review by Dr. Iglesia on agents that are used to demonstrate ureteral patency. I like phenazopyridine because it is cheap and readily available. It works great if you remember one thing: drain the bladder first so the orange color stands out in the colorless saline irrigant. Otherwise, the orange-dyed urine obscures the orange ureteral jets.
John H. Sand, MD
Ellensburg, Washington
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Tip for when using phenazophyridine
I enjoyed the review by Dr. Iglesia on agents that are used to demonstrate ureteral patency. I like phenazopyridine because it is cheap and readily available. It works great if you remember one thing: drain the bladder first so the orange color stands out in the colorless saline irrigant. Otherwise, the orange-dyed urine obscures the orange ureteral jets.
John H. Sand, MD
Ellensburg, Washington
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Tip for when using phenazophyridine
I enjoyed the review by Dr. Iglesia on agents that are used to demonstrate ureteral patency. I like phenazopyridine because it is cheap and readily available. It works great if you remember one thing: drain the bladder first so the orange color stands out in the colorless saline irrigant. Otherwise, the orange-dyed urine obscures the orange ureteral jets.
John H. Sand, MD
Ellensburg, Washington
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Emergency gout admission increase is ‘call to arms’
LIVERPOOL, ENGLAND – The rate of emergency hospital admissions for gout in England has seen a 59% increase over the past decade, while that of rheumatoid arthritis has halved, it was reported at the British Society for Rheumatology annual conference.
Over an approximate 10-year period (2006-2017), the incidence rate of unplanned gout admissions increased from 7.9 to 12.5 admissions per 100,000 of the population. This represented an increase from 0.023% to 0.032% of all hospital admissions during the period.
To put that into perspective, unplanned admissions for rheumatoid arthritis (RA), decreased from 8.6 to 4.3 admissions per 100,000 of the population, said Mark D. Russell, MD, a rheumatology registrar at Guy’s and St Thomas’ Hospital in London.
Furthermore, primary care prescriptions for common gout medications have seen a dramatic increase over the same time period in England; allopurinol prescriptions are up 72%, there’s been a 166% increase in colchicine prescriptions, and a 20-fold increase in febuxostat (Uloric) prescriptions since data became available for its in 2010.
“Gout’s very much a treatable condition,” Dr. Russell said, but with 82% of all gout admissions being unplanned, “there’s clearly more to do; this should be a call to arms for rheumatologists to help reduce the in-patient burden of this condition.”
The mean length of hospital stay was estimated at 6.6 days, with the median being 3.2 days. Gout accounted for just under 350,000 hospital bed days from 2006 to 2017, and with the cost of a single gout admission being anything from £850 up to £5,600, it constitutes a significant burden for the country’s National Health Service.
But what can be done? Would a “door-to-needle time campaign” help? So that when patients attend the emergency department they are assessed rapidly and treated accordingly? Dr. Russell queried.
Education could be the key, was the consensus during the discussion following his presentation. Education, and not just of those affected by the condition, but also of the family physicians who seem to have a “knee-jerk reaction” to prescribe medications, and not always appropriately. Even hospital staff may need help in differentiating gout from other emergency presentations, with some admitting patients suspecting infection or wrongly discharging them.
Pharmacist-led gout clinics
Another approach to try to avoid emergency hospital visits could be better management and perhaps setting up specialist gout clinics. Such clinics have already been piloted, and rheumatology pharmacist Jane Whiteman shared her experience of setting up a monthly, pharmacist-led gout clinic in a separate presentation.
Dr. Whiteman, who works at Royal Victoria Hospital, part of the Belfast Health and Social Care Trust in Ireland, presented data on 52 patients who were seen at the clinic between June 2015 and May 2017. The total number of patient visits was 87, with an average of 1.7 visits per patient.
Of 38 patients who were discharged from the clinic, 29 (76%) had met target levels of serum uric acid, which guidelines from the British Society for Rheumatology set at less than 0.3 mmol/L (5 mg/dL) and those from the European League of Rheumatism set at less than 0.36 mmol/L (6 mg/dL).
It is important to reduce serum uric acid levels, Dr. Whiteman explained. “Gout occurs when serum uric acid rises and urate crystals reach their saturation point in the serum and start to crystallize out into the joints and into the tissues,” she said. “It’s a progressive disease that usually starts in one joint, but if the serum uric acid isn’t controlled then it can go on to affect a number of joints,” and cause chronic arthritis, among other potentially serious conditions, and is an independent risk factor for cardiovascular and renal disease.
“Studies across the world have shown that gout is not well looked after; patient adherence to treatment is very poor,” Dr. Whiteman said. “Among all the chronic diseases it has the lowest adherence to treatment,” she added, noting that one study showed just one-fifth of patients remained on gout medication at 1 year.
Patient education is an important part of the clinic’s services, as when people are asymptomatic and between bouts of gout, they perhaps do not realize that they still need to take their medication. Education thus needs to include talking about their diet and lifestyle, providing information on medication, and why it is important to keep their serum uric acid levels in check.
After patients’ initial referral to the clinic, they are followed up by the clinic every month until their serum urate levels are below the 0.3 mmol/L target. They can then be discharged and monitored by their family physician.
Postdischarge, Dr. Whiteman and her colleagues found that 22 (76%) of the 29 patients who had met their target levels of serum uric acid later had serum uric acid tested at least once, showing an average level of 0.29 mmol/L at follow-up. This reassuring result occurred perhaps because of a majority of patients (79%) who were still being prescribed, and presumably taking, urate-lowering therapy. Seven patients did not undergo follow-up serum uric acid testing because they had died (one), were in the hospital (one), were not taking medication because they had made diet or lifestyle changes (three), or had their treatment on hold (two).
“I think the gout clinic has been a success; it has addressed barriers to optimal management through education of the patient,” Dr. Whiteman said.
Both presenters had nothing to disclose.
SOURCE: Russel M et al. Rheumatology. 2018;57[Suppl. 3]:key075.186; Whiteman J, et al. Rheumatology. 2018;57[Suppl. 3]:key075.215.
LIVERPOOL, ENGLAND – The rate of emergency hospital admissions for gout in England has seen a 59% increase over the past decade, while that of rheumatoid arthritis has halved, it was reported at the British Society for Rheumatology annual conference.
Over an approximate 10-year period (2006-2017), the incidence rate of unplanned gout admissions increased from 7.9 to 12.5 admissions per 100,000 of the population. This represented an increase from 0.023% to 0.032% of all hospital admissions during the period.
To put that into perspective, unplanned admissions for rheumatoid arthritis (RA), decreased from 8.6 to 4.3 admissions per 100,000 of the population, said Mark D. Russell, MD, a rheumatology registrar at Guy’s and St Thomas’ Hospital in London.
Furthermore, primary care prescriptions for common gout medications have seen a dramatic increase over the same time period in England; allopurinol prescriptions are up 72%, there’s been a 166% increase in colchicine prescriptions, and a 20-fold increase in febuxostat (Uloric) prescriptions since data became available for its in 2010.
“Gout’s very much a treatable condition,” Dr. Russell said, but with 82% of all gout admissions being unplanned, “there’s clearly more to do; this should be a call to arms for rheumatologists to help reduce the in-patient burden of this condition.”
The mean length of hospital stay was estimated at 6.6 days, with the median being 3.2 days. Gout accounted for just under 350,000 hospital bed days from 2006 to 2017, and with the cost of a single gout admission being anything from £850 up to £5,600, it constitutes a significant burden for the country’s National Health Service.
But what can be done? Would a “door-to-needle time campaign” help? So that when patients attend the emergency department they are assessed rapidly and treated accordingly? Dr. Russell queried.
Education could be the key, was the consensus during the discussion following his presentation. Education, and not just of those affected by the condition, but also of the family physicians who seem to have a “knee-jerk reaction” to prescribe medications, and not always appropriately. Even hospital staff may need help in differentiating gout from other emergency presentations, with some admitting patients suspecting infection or wrongly discharging them.
Pharmacist-led gout clinics
Another approach to try to avoid emergency hospital visits could be better management and perhaps setting up specialist gout clinics. Such clinics have already been piloted, and rheumatology pharmacist Jane Whiteman shared her experience of setting up a monthly, pharmacist-led gout clinic in a separate presentation.
Dr. Whiteman, who works at Royal Victoria Hospital, part of the Belfast Health and Social Care Trust in Ireland, presented data on 52 patients who were seen at the clinic between June 2015 and May 2017. The total number of patient visits was 87, with an average of 1.7 visits per patient.
Of 38 patients who were discharged from the clinic, 29 (76%) had met target levels of serum uric acid, which guidelines from the British Society for Rheumatology set at less than 0.3 mmol/L (5 mg/dL) and those from the European League of Rheumatism set at less than 0.36 mmol/L (6 mg/dL).
It is important to reduce serum uric acid levels, Dr. Whiteman explained. “Gout occurs when serum uric acid rises and urate crystals reach their saturation point in the serum and start to crystallize out into the joints and into the tissues,” she said. “It’s a progressive disease that usually starts in one joint, but if the serum uric acid isn’t controlled then it can go on to affect a number of joints,” and cause chronic arthritis, among other potentially serious conditions, and is an independent risk factor for cardiovascular and renal disease.
“Studies across the world have shown that gout is not well looked after; patient adherence to treatment is very poor,” Dr. Whiteman said. “Among all the chronic diseases it has the lowest adherence to treatment,” she added, noting that one study showed just one-fifth of patients remained on gout medication at 1 year.
Patient education is an important part of the clinic’s services, as when people are asymptomatic and between bouts of gout, they perhaps do not realize that they still need to take their medication. Education thus needs to include talking about their diet and lifestyle, providing information on medication, and why it is important to keep their serum uric acid levels in check.
After patients’ initial referral to the clinic, they are followed up by the clinic every month until their serum urate levels are below the 0.3 mmol/L target. They can then be discharged and monitored by their family physician.
Postdischarge, Dr. Whiteman and her colleagues found that 22 (76%) of the 29 patients who had met their target levels of serum uric acid later had serum uric acid tested at least once, showing an average level of 0.29 mmol/L at follow-up. This reassuring result occurred perhaps because of a majority of patients (79%) who were still being prescribed, and presumably taking, urate-lowering therapy. Seven patients did not undergo follow-up serum uric acid testing because they had died (one), were in the hospital (one), were not taking medication because they had made diet or lifestyle changes (three), or had their treatment on hold (two).
“I think the gout clinic has been a success; it has addressed barriers to optimal management through education of the patient,” Dr. Whiteman said.
Both presenters had nothing to disclose.
SOURCE: Russel M et al. Rheumatology. 2018;57[Suppl. 3]:key075.186; Whiteman J, et al. Rheumatology. 2018;57[Suppl. 3]:key075.215.
LIVERPOOL, ENGLAND – The rate of emergency hospital admissions for gout in England has seen a 59% increase over the past decade, while that of rheumatoid arthritis has halved, it was reported at the British Society for Rheumatology annual conference.
Over an approximate 10-year period (2006-2017), the incidence rate of unplanned gout admissions increased from 7.9 to 12.5 admissions per 100,000 of the population. This represented an increase from 0.023% to 0.032% of all hospital admissions during the period.
To put that into perspective, unplanned admissions for rheumatoid arthritis (RA), decreased from 8.6 to 4.3 admissions per 100,000 of the population, said Mark D. Russell, MD, a rheumatology registrar at Guy’s and St Thomas’ Hospital in London.
Furthermore, primary care prescriptions for common gout medications have seen a dramatic increase over the same time period in England; allopurinol prescriptions are up 72%, there’s been a 166% increase in colchicine prescriptions, and a 20-fold increase in febuxostat (Uloric) prescriptions since data became available for its in 2010.
“Gout’s very much a treatable condition,” Dr. Russell said, but with 82% of all gout admissions being unplanned, “there’s clearly more to do; this should be a call to arms for rheumatologists to help reduce the in-patient burden of this condition.”
The mean length of hospital stay was estimated at 6.6 days, with the median being 3.2 days. Gout accounted for just under 350,000 hospital bed days from 2006 to 2017, and with the cost of a single gout admission being anything from £850 up to £5,600, it constitutes a significant burden for the country’s National Health Service.
But what can be done? Would a “door-to-needle time campaign” help? So that when patients attend the emergency department they are assessed rapidly and treated accordingly? Dr. Russell queried.
Education could be the key, was the consensus during the discussion following his presentation. Education, and not just of those affected by the condition, but also of the family physicians who seem to have a “knee-jerk reaction” to prescribe medications, and not always appropriately. Even hospital staff may need help in differentiating gout from other emergency presentations, with some admitting patients suspecting infection or wrongly discharging them.
Pharmacist-led gout clinics
Another approach to try to avoid emergency hospital visits could be better management and perhaps setting up specialist gout clinics. Such clinics have already been piloted, and rheumatology pharmacist Jane Whiteman shared her experience of setting up a monthly, pharmacist-led gout clinic in a separate presentation.
Dr. Whiteman, who works at Royal Victoria Hospital, part of the Belfast Health and Social Care Trust in Ireland, presented data on 52 patients who were seen at the clinic between June 2015 and May 2017. The total number of patient visits was 87, with an average of 1.7 visits per patient.
Of 38 patients who were discharged from the clinic, 29 (76%) had met target levels of serum uric acid, which guidelines from the British Society for Rheumatology set at less than 0.3 mmol/L (5 mg/dL) and those from the European League of Rheumatism set at less than 0.36 mmol/L (6 mg/dL).
It is important to reduce serum uric acid levels, Dr. Whiteman explained. “Gout occurs when serum uric acid rises and urate crystals reach their saturation point in the serum and start to crystallize out into the joints and into the tissues,” she said. “It’s a progressive disease that usually starts in one joint, but if the serum uric acid isn’t controlled then it can go on to affect a number of joints,” and cause chronic arthritis, among other potentially serious conditions, and is an independent risk factor for cardiovascular and renal disease.
“Studies across the world have shown that gout is not well looked after; patient adherence to treatment is very poor,” Dr. Whiteman said. “Among all the chronic diseases it has the lowest adherence to treatment,” she added, noting that one study showed just one-fifth of patients remained on gout medication at 1 year.
Patient education is an important part of the clinic’s services, as when people are asymptomatic and between bouts of gout, they perhaps do not realize that they still need to take their medication. Education thus needs to include talking about their diet and lifestyle, providing information on medication, and why it is important to keep their serum uric acid levels in check.
After patients’ initial referral to the clinic, they are followed up by the clinic every month until their serum urate levels are below the 0.3 mmol/L target. They can then be discharged and monitored by their family physician.
Postdischarge, Dr. Whiteman and her colleagues found that 22 (76%) of the 29 patients who had met their target levels of serum uric acid later had serum uric acid tested at least once, showing an average level of 0.29 mmol/L at follow-up. This reassuring result occurred perhaps because of a majority of patients (79%) who were still being prescribed, and presumably taking, urate-lowering therapy. Seven patients did not undergo follow-up serum uric acid testing because they had died (one), were in the hospital (one), were not taking medication because they had made diet or lifestyle changes (three), or had their treatment on hold (two).
“I think the gout clinic has been a success; it has addressed barriers to optimal management through education of the patient,” Dr. Whiteman said.
Both presenters had nothing to disclose.
SOURCE: Russel M et al. Rheumatology. 2018;57[Suppl. 3]:key075.186; Whiteman J, et al. Rheumatology. 2018;57[Suppl. 3]:key075.215.
AT RHEUMATOLOGY 2018
Key clinical point:
Major finding: The rate of emergency hospital admissions for gout in England increased by 59%, from 7.9 to 12.5 admissions per 100,000 of the population; 76% of patients attending a pharmacist-led gout clinic achieved target serum uric acid levels.
Study details: An analysis of National Health Service data from April 2006 to March 2017 on hospital admissions for gout and primary care prescription data and a separate study of 52 patients attending a pharmacist-led gout clinic.
Disclosures: Both presenters had nothing to disclose.
Sources: Russell M et al. Rheumatology. 2018;57[Suppl. 3]:key075.186; Whiteman J et al. Rheumatology. 2018;57[Suppl. 3]:key075.215.
Rash goes undetected
Rash goes undetected
As a urogynecologist, in the past 5 years I have had 2 urgent emergency department referrals from 2 towns. The patients had excruciating flank pain and had a negative computed tomography scan and normal pelvic and renal examinations, but no physical exam. They were subsequently found to have shingles!
Bunan Alnaif, MD
Chesapeake, Virginia
Physical exam revealed suspicious mass
Two years ago a regular gynecologic patient of mine came in 2 months early for her Pap test because she was concerned about a pressure in her genital area. I had delivered her 3 children. She was now in her mid-40s. She had visited her usual physician about the problem; she was not physically examined but was advised to see a gastrointestinal specialist, since the pressure caused constipation with discomfort. She then consulted a gastroenterologist, who performed a colonoscopy that was reported as normal. The patient related that she had no pelvic or rectal examination at that time, although it is possible that one could have been done while she was under anesthesia.
She arrived at my office 3 weeks later, and while doing the pelvic and rectal exam, I noted she had a 3- to 4-cm perirectal mass, which I thought was a Bartholin’s tumor. I referred her to a gynecologic oncologist who happened to write a paper on this subject. My diagnosis was wrong—she had a rectal carcinoma, which fortunately was Stage 1.
The patient subsequently has done well. The delay in diagnosis could have been averted if a simple rectal examination had been performed by the first doctor.
James Moran, MD
Santa Monica, California
Case of an almost missed diagnosis
I have many examples of how not performing a physical examination can cause problems, but here is a recent one. This involved a 70-year-old woman who had been seeing only her primary care physician for the past 30 years, with no pelvic examinations done. She had symptoms of vaginal discharge and itch for which she was given multiple courses of antifungals and topical steroids. Finally, she was referred to me. Examination revealed findings of extensive raised, erythematous, hyperkeratotic, macerated lesions throughout the vulva. A punch biopsy revealed severe vulvar dysplasia with areas suspicious for squamous cell carcinoma. I referred the patient to a gynecologic oncologist, who performed a simple vulvectomy. There were extensive foci of vulvar intraepithelial neoplasia 3.
Susan Richman, MD
New Haven, Connecticut
Lack of physical exam leads to tortuous dx course
Here is a story of a patient who must have gone without having a pelvic examination or any evaluation for years. This 83-year-old woman had a previous transvaginal hysterectomy at age 49 for fibroids and bleeding. She is quite healthy and active for her age. She had problems with recurrent urinary tract infection for several years before being referred to a gynecologist. She had emergency room visits and multiple urgent care visits. She saw her primary care physician 3 times in 4 weeks for bladder pain and a sensation of incomplete bladder emptying. She reported that when she got up in the morning, it felt like her urine slowly leaked out for several hours. She was referred to a urologist, who saw her twice and did pelvic ultrasonography and postvoid residual urine testing—without a pelvic exam.
After 2 months of regular visits, an examination by her primary care physician revealed a complete fusion of the labia. Six months after her initial urology visit, the patient had an examination with a plan for cystoscopy, and the urologist ended up doing a “dilation of labial fusion” in the office. The patient’s urinary symptoms were improved slightly, and she had visits to the emergency room or urgent care once monthly for dysuria after dilation of the labia.
At that point she was referred to me. We tried topical estrogen for several months with minimal improvement in symptoms, and I performed a surgical separation of labial fusion in the operating room under monitored anesthesia care. After surgery the patient said that she felt like “I got my life back,” and she never knew how happy she could be to pee in the morning.
Theresa Gipps, MD
Walnut Creek, California
Agrees with importance of clinical exam
I fully agree that clinical examination skill is a dying art. But the American College of Obstetricians and Gynecologists has issued guidelines stating that pelvic examination is not required, especially in asymptomatic women. Another area of concern is hair removal procedures like waxing and laser treatments in the pubic area, and whether these do harm in any way or increase the likelihood of skin problems.
Manju Hotchandani, MD
New Delhi, India
Dr. Barbieri responds
I thank Drs. Alnaif, Moran, Richman, Gipps, and Hotchandani for sharing their comments and important clinical vignettes concerning the primacy of the physical examination with our readers. In clinical practice there are many competing demands on the time of clinicians, but we should strive to preserve time for a good physical examination. If not us, who is going to perform a competent physical examination?
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Rash goes undetected
As a urogynecologist, in the past 5 years I have had 2 urgent emergency department referrals from 2 towns. The patients had excruciating flank pain and had a negative computed tomography scan and normal pelvic and renal examinations, but no physical exam. They were subsequently found to have shingles!
Bunan Alnaif, MD
Chesapeake, Virginia
Physical exam revealed suspicious mass
Two years ago a regular gynecologic patient of mine came in 2 months early for her Pap test because she was concerned about a pressure in her genital area. I had delivered her 3 children. She was now in her mid-40s. She had visited her usual physician about the problem; she was not physically examined but was advised to see a gastrointestinal specialist, since the pressure caused constipation with discomfort. She then consulted a gastroenterologist, who performed a colonoscopy that was reported as normal. The patient related that she had no pelvic or rectal examination at that time, although it is possible that one could have been done while she was under anesthesia.
She arrived at my office 3 weeks later, and while doing the pelvic and rectal exam, I noted she had a 3- to 4-cm perirectal mass, which I thought was a Bartholin’s tumor. I referred her to a gynecologic oncologist who happened to write a paper on this subject. My diagnosis was wrong—she had a rectal carcinoma, which fortunately was Stage 1.
The patient subsequently has done well. The delay in diagnosis could have been averted if a simple rectal examination had been performed by the first doctor.
James Moran, MD
Santa Monica, California
Case of an almost missed diagnosis
I have many examples of how not performing a physical examination can cause problems, but here is a recent one. This involved a 70-year-old woman who had been seeing only her primary care physician for the past 30 years, with no pelvic examinations done. She had symptoms of vaginal discharge and itch for which she was given multiple courses of antifungals and topical steroids. Finally, she was referred to me. Examination revealed findings of extensive raised, erythematous, hyperkeratotic, macerated lesions throughout the vulva. A punch biopsy revealed severe vulvar dysplasia with areas suspicious for squamous cell carcinoma. I referred the patient to a gynecologic oncologist, who performed a simple vulvectomy. There were extensive foci of vulvar intraepithelial neoplasia 3.
Susan Richman, MD
New Haven, Connecticut
Lack of physical exam leads to tortuous dx course
Here is a story of a patient who must have gone without having a pelvic examination or any evaluation for years. This 83-year-old woman had a previous transvaginal hysterectomy at age 49 for fibroids and bleeding. She is quite healthy and active for her age. She had problems with recurrent urinary tract infection for several years before being referred to a gynecologist. She had emergency room visits and multiple urgent care visits. She saw her primary care physician 3 times in 4 weeks for bladder pain and a sensation of incomplete bladder emptying. She reported that when she got up in the morning, it felt like her urine slowly leaked out for several hours. She was referred to a urologist, who saw her twice and did pelvic ultrasonography and postvoid residual urine testing—without a pelvic exam.
After 2 months of regular visits, an examination by her primary care physician revealed a complete fusion of the labia. Six months after her initial urology visit, the patient had an examination with a plan for cystoscopy, and the urologist ended up doing a “dilation of labial fusion” in the office. The patient’s urinary symptoms were improved slightly, and she had visits to the emergency room or urgent care once monthly for dysuria after dilation of the labia.
At that point she was referred to me. We tried topical estrogen for several months with minimal improvement in symptoms, and I performed a surgical separation of labial fusion in the operating room under monitored anesthesia care. After surgery the patient said that she felt like “I got my life back,” and she never knew how happy she could be to pee in the morning.
Theresa Gipps, MD
Walnut Creek, California
Agrees with importance of clinical exam
I fully agree that clinical examination skill is a dying art. But the American College of Obstetricians and Gynecologists has issued guidelines stating that pelvic examination is not required, especially in asymptomatic women. Another area of concern is hair removal procedures like waxing and laser treatments in the pubic area, and whether these do harm in any way or increase the likelihood of skin problems.
Manju Hotchandani, MD
New Delhi, India
Dr. Barbieri responds
I thank Drs. Alnaif, Moran, Richman, Gipps, and Hotchandani for sharing their comments and important clinical vignettes concerning the primacy of the physical examination with our readers. In clinical practice there are many competing demands on the time of clinicians, but we should strive to preserve time for a good physical examination. If not us, who is going to perform a competent physical examination?
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Rash goes undetected
As a urogynecologist, in the past 5 years I have had 2 urgent emergency department referrals from 2 towns. The patients had excruciating flank pain and had a negative computed tomography scan and normal pelvic and renal examinations, but no physical exam. They were subsequently found to have shingles!
Bunan Alnaif, MD
Chesapeake, Virginia
Physical exam revealed suspicious mass
Two years ago a regular gynecologic patient of mine came in 2 months early for her Pap test because she was concerned about a pressure in her genital area. I had delivered her 3 children. She was now in her mid-40s. She had visited her usual physician about the problem; she was not physically examined but was advised to see a gastrointestinal specialist, since the pressure caused constipation with discomfort. She then consulted a gastroenterologist, who performed a colonoscopy that was reported as normal. The patient related that she had no pelvic or rectal examination at that time, although it is possible that one could have been done while she was under anesthesia.
She arrived at my office 3 weeks later, and while doing the pelvic and rectal exam, I noted she had a 3- to 4-cm perirectal mass, which I thought was a Bartholin’s tumor. I referred her to a gynecologic oncologist who happened to write a paper on this subject. My diagnosis was wrong—she had a rectal carcinoma, which fortunately was Stage 1.
The patient subsequently has done well. The delay in diagnosis could have been averted if a simple rectal examination had been performed by the first doctor.
James Moran, MD
Santa Monica, California
Case of an almost missed diagnosis
I have many examples of how not performing a physical examination can cause problems, but here is a recent one. This involved a 70-year-old woman who had been seeing only her primary care physician for the past 30 years, with no pelvic examinations done. She had symptoms of vaginal discharge and itch for which she was given multiple courses of antifungals and topical steroids. Finally, she was referred to me. Examination revealed findings of extensive raised, erythematous, hyperkeratotic, macerated lesions throughout the vulva. A punch biopsy revealed severe vulvar dysplasia with areas suspicious for squamous cell carcinoma. I referred the patient to a gynecologic oncologist, who performed a simple vulvectomy. There were extensive foci of vulvar intraepithelial neoplasia 3.
Susan Richman, MD
New Haven, Connecticut
Lack of physical exam leads to tortuous dx course
Here is a story of a patient who must have gone without having a pelvic examination or any evaluation for years. This 83-year-old woman had a previous transvaginal hysterectomy at age 49 for fibroids and bleeding. She is quite healthy and active for her age. She had problems with recurrent urinary tract infection for several years before being referred to a gynecologist. She had emergency room visits and multiple urgent care visits. She saw her primary care physician 3 times in 4 weeks for bladder pain and a sensation of incomplete bladder emptying. She reported that when she got up in the morning, it felt like her urine slowly leaked out for several hours. She was referred to a urologist, who saw her twice and did pelvic ultrasonography and postvoid residual urine testing—without a pelvic exam.
After 2 months of regular visits, an examination by her primary care physician revealed a complete fusion of the labia. Six months after her initial urology visit, the patient had an examination with a plan for cystoscopy, and the urologist ended up doing a “dilation of labial fusion” in the office. The patient’s urinary symptoms were improved slightly, and she had visits to the emergency room or urgent care once monthly for dysuria after dilation of the labia.
At that point she was referred to me. We tried topical estrogen for several months with minimal improvement in symptoms, and I performed a surgical separation of labial fusion in the operating room under monitored anesthesia care. After surgery the patient said that she felt like “I got my life back,” and she never knew how happy she could be to pee in the morning.
Theresa Gipps, MD
Walnut Creek, California
Agrees with importance of clinical exam
I fully agree that clinical examination skill is a dying art. But the American College of Obstetricians and Gynecologists has issued guidelines stating that pelvic examination is not required, especially in asymptomatic women. Another area of concern is hair removal procedures like waxing and laser treatments in the pubic area, and whether these do harm in any way or increase the likelihood of skin problems.
Manju Hotchandani, MD
New Delhi, India
Dr. Barbieri responds
I thank Drs. Alnaif, Moran, Richman, Gipps, and Hotchandani for sharing their comments and important clinical vignettes concerning the primacy of the physical examination with our readers. In clinical practice there are many competing demands on the time of clinicians, but we should strive to preserve time for a good physical examination. If not us, who is going to perform a competent physical examination?
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Treatment includes surgery
Treatment includes surgery
Thank you for the great article about hidradenitis suppurativa. It was very informative as usual, but a little shortsighted. As ObGyns we tend not to focus so much on these dermatologic conditions. However, I think something very important is missing in the article. I do not see it mentioned that hidradenitis suppurativa is a type of acne, also called acne inversa. As such, it should be treated like acne, with special attention to diet with zero dairy products as a prevention measure. Also, metformin is very important, as noted in the article. Retinoids are also needed, maybe for years.
According to experts, the primary approach to this condition is surgical, with punch biopsies and unroofing of the lesions, with medical therapies as prevention strategies. Fortunately, special task forces are now tackling this condition, especially in Europe. I strongly recommend the book, Acne: Causes and Practical Management, by F. William Danby.
Ivan Valencia, MD
Quito, Ecuador
Dr. Barbieri responds
Dr. Valencia provides an important perspective on the surgical treatment of hidradenitis suppurativa (HS). I agree that surgery is an important treatment for Stage III HS, but nonsurgical approaches are preferred and often effective for Stage I HS, a stage most likely to be treated by a gynecologist.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Treatment includes surgery
Thank you for the great article about hidradenitis suppurativa. It was very informative as usual, but a little shortsighted. As ObGyns we tend not to focus so much on these dermatologic conditions. However, I think something very important is missing in the article. I do not see it mentioned that hidradenitis suppurativa is a type of acne, also called acne inversa. As such, it should be treated like acne, with special attention to diet with zero dairy products as a prevention measure. Also, metformin is very important, as noted in the article. Retinoids are also needed, maybe for years.
According to experts, the primary approach to this condition is surgical, with punch biopsies and unroofing of the lesions, with medical therapies as prevention strategies. Fortunately, special task forces are now tackling this condition, especially in Europe. I strongly recommend the book, Acne: Causes and Practical Management, by F. William Danby.
Ivan Valencia, MD
Quito, Ecuador
Dr. Barbieri responds
Dr. Valencia provides an important perspective on the surgical treatment of hidradenitis suppurativa (HS). I agree that surgery is an important treatment for Stage III HS, but nonsurgical approaches are preferred and often effective for Stage I HS, a stage most likely to be treated by a gynecologist.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Treatment includes surgery
Thank you for the great article about hidradenitis suppurativa. It was very informative as usual, but a little shortsighted. As ObGyns we tend not to focus so much on these dermatologic conditions. However, I think something very important is missing in the article. I do not see it mentioned that hidradenitis suppurativa is a type of acne, also called acne inversa. As such, it should be treated like acne, with special attention to diet with zero dairy products as a prevention measure. Also, metformin is very important, as noted in the article. Retinoids are also needed, maybe for years.
According to experts, the primary approach to this condition is surgical, with punch biopsies and unroofing of the lesions, with medical therapies as prevention strategies. Fortunately, special task forces are now tackling this condition, especially in Europe. I strongly recommend the book, Acne: Causes and Practical Management, by F. William Danby.
Ivan Valencia, MD
Quito, Ecuador
Dr. Barbieri responds
Dr. Valencia provides an important perspective on the surgical treatment of hidradenitis suppurativa (HS). I agree that surgery is an important treatment for Stage III HS, but nonsurgical approaches are preferred and often effective for Stage I HS, a stage most likely to be treated by a gynecologist.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Incision site for cesarean delivery is important in infection prevention
Incision site for cesarean delivery is important in infection prevention
Dr. Barbieri’s editorial very nicely explained strategies to reduce the risk of post–cesarean delivery surgical site infection (SSI). However, what was not mentioned, in my opinion, is the most important preventive strategy. Selecting the site for the initial skin incision plays a great role in whether or not the patient will develop an infection postoperatively.
Pfannenstiel incisions are popular because of their obvious cosmetic benefit. In nonemergent cesarean deliveries, most ObGyns try to use this incision. However, exactly where the incision is placed plays a large role in the genesis of a postoperative wound infection. The worst place for such incisions is in the crease above the pubis and below the panniculus. Invariably, this area remains moist and macerated, especially in obese patients, thus providing a fertile breeding ground for bacteria. This problem can be avoided by incising the skin approximately 2 cm cranial to and parallel to the aforementioned crease, provided that the panniculus is not too large. The point is that the incision should be placed in an area where it has a chance to stay dry.
Sometimes patients who are hugely obese require great creativity in the placement of their transverse skin incision. I recall one patient, pregnant with triplets, whose abdomen was so large that her umbilicus was over the region of the lower uterine segment when she was supine on the operating room table. Some would have lifted up her immense panniculus and placed the incision in the usual crease site. This would be problematic for obtaining adequate exposure to deliver the babies, and the risk of developing an incisional infection would be very high. Therefore, a transverse incision was made just below her umbilicus. The panniculus was a nonissue regarding gaining adequate exposure and, when closed, the incision remained completely dry and uninfected. The patient did extremely well postoperatively and had no infectious sequelae.
David L. Zisow, MD
Baltimore, Maryland
Extraperitoneal approach should be considered
I enjoyed the editorial on reducing surgical site infection, especially the references to the historical Halsted principles of surgery. “He was the first in this country to promulgate the philosophy of ‘safe’ surgery.”1 Regarding surgical principles of cesarean delivery, the pioneering German obstetricians in the 1930s were keenly aware that avoiding the peritoneal cavity was instrumental in reducing morbidity and mortality. They championed the safety of the extraperitoneal approach as the fundamental principle of cesarean delivery for maternal safety.2
I learned to embrace the principles of Kaboth while learning the technique in 1968–1972. Thus, for more than 30 years, I used the extraperitoneal approach to access the lower uterine segment, avoiding entrance into the abdominal cavity. My patients seemed to benefit. As the surgeon, I also benefited: with short operative delivery times, less postoperative pain and minor morbidities, fewer phone calls from nursing staff, and less difficulty for my patients. I had not contaminated the peritoneal cavity and avoided all those inherent problems. The decision to open the peritoneal cavity has not been subjected to the rigors of critical analysis.3 I think that Kaboth’s principles remain worthy of consideration even today.
Contemporary experiences in large populations such as in India and China that use the extraperitoneal cesarean approach seem to implicitly support Kaboth’s principles. However, in the milieu of evidence-based medicine, extraperitoneal cesarean delivery has not been adequately studied.4 Just maybe the extraperitoneal approach should be considered and understood as a primary surgical technique for cesarean deliveries; just maybe it deserves a historical asterisk alongside the Halsted dicta.
Hedric Hanson, MD
Anchorage, Alaska
Dr. Barbieri responds
I thank Drs. Zisow and Hanson for their great recommendations and clinical pearls. I agree with Dr. Zisow that I should have mentioned the importance of optimal placement of the transverse skin incision. Incision in a skin crease that is perpetually moist increases the risk for a postoperative complication. When the abdomen is prepped for surgery, the skin crease above the pubis appears to be very inviting for placement of the skin incision. Dr. Hanson highlights the important option of an extraperitoneal approach to cesarean delivery. I have not thought about using this approach since the mid-1980s. Dr. Hanson’s recommendation that a randomized trial be performed comparing the SSI rate and other outcomes for extraperitoneal and intraperitoneal cesarean delivery is a great idea.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Cameron JL. William Steward Halsted: our surgical heritage. Ann Surg. 1997;225(5):445–458.
- Kaboth G. Die Technik des extraperitonealen Entibindungschnittes. Zentralblatt fur Gynakologie.1934;58(6):310–311.
- Berghella V, Baxter JK Chauhan SP. Evidence-based surgery for cesarean section. Am J Obstet Gynecol. 2005;193(5):1607–1617.
- Hofmeyr GJ, Mathai M, Shah AN, Novikova N. Techniques for caesarean section. Cochrane Database Syst Rev. 2008; CD004662.
Incision site for cesarean delivery is important in infection prevention
Dr. Barbieri’s editorial very nicely explained strategies to reduce the risk of post–cesarean delivery surgical site infection (SSI). However, what was not mentioned, in my opinion, is the most important preventive strategy. Selecting the site for the initial skin incision plays a great role in whether or not the patient will develop an infection postoperatively.
Pfannenstiel incisions are popular because of their obvious cosmetic benefit. In nonemergent cesarean deliveries, most ObGyns try to use this incision. However, exactly where the incision is placed plays a large role in the genesis of a postoperative wound infection. The worst place for such incisions is in the crease above the pubis and below the panniculus. Invariably, this area remains moist and macerated, especially in obese patients, thus providing a fertile breeding ground for bacteria. This problem can be avoided by incising the skin approximately 2 cm cranial to and parallel to the aforementioned crease, provided that the panniculus is not too large. The point is that the incision should be placed in an area where it has a chance to stay dry.
Sometimes patients who are hugely obese require great creativity in the placement of their transverse skin incision. I recall one patient, pregnant with triplets, whose abdomen was so large that her umbilicus was over the region of the lower uterine segment when she was supine on the operating room table. Some would have lifted up her immense panniculus and placed the incision in the usual crease site. This would be problematic for obtaining adequate exposure to deliver the babies, and the risk of developing an incisional infection would be very high. Therefore, a transverse incision was made just below her umbilicus. The panniculus was a nonissue regarding gaining adequate exposure and, when closed, the incision remained completely dry and uninfected. The patient did extremely well postoperatively and had no infectious sequelae.
David L. Zisow, MD
Baltimore, Maryland
Extraperitoneal approach should be considered
I enjoyed the editorial on reducing surgical site infection, especially the references to the historical Halsted principles of surgery. “He was the first in this country to promulgate the philosophy of ‘safe’ surgery.”1 Regarding surgical principles of cesarean delivery, the pioneering German obstetricians in the 1930s were keenly aware that avoiding the peritoneal cavity was instrumental in reducing morbidity and mortality. They championed the safety of the extraperitoneal approach as the fundamental principle of cesarean delivery for maternal safety.2
I learned to embrace the principles of Kaboth while learning the technique in 1968–1972. Thus, for more than 30 years, I used the extraperitoneal approach to access the lower uterine segment, avoiding entrance into the abdominal cavity. My patients seemed to benefit. As the surgeon, I also benefited: with short operative delivery times, less postoperative pain and minor morbidities, fewer phone calls from nursing staff, and less difficulty for my patients. I had not contaminated the peritoneal cavity and avoided all those inherent problems. The decision to open the peritoneal cavity has not been subjected to the rigors of critical analysis.3 I think that Kaboth’s principles remain worthy of consideration even today.
Contemporary experiences in large populations such as in India and China that use the extraperitoneal cesarean approach seem to implicitly support Kaboth’s principles. However, in the milieu of evidence-based medicine, extraperitoneal cesarean delivery has not been adequately studied.4 Just maybe the extraperitoneal approach should be considered and understood as a primary surgical technique for cesarean deliveries; just maybe it deserves a historical asterisk alongside the Halsted dicta.
Hedric Hanson, MD
Anchorage, Alaska
Dr. Barbieri responds
I thank Drs. Zisow and Hanson for their great recommendations and clinical pearls. I agree with Dr. Zisow that I should have mentioned the importance of optimal placement of the transverse skin incision. Incision in a skin crease that is perpetually moist increases the risk for a postoperative complication. When the abdomen is prepped for surgery, the skin crease above the pubis appears to be very inviting for placement of the skin incision. Dr. Hanson highlights the important option of an extraperitoneal approach to cesarean delivery. I have not thought about using this approach since the mid-1980s. Dr. Hanson’s recommendation that a randomized trial be performed comparing the SSI rate and other outcomes for extraperitoneal and intraperitoneal cesarean delivery is a great idea.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Incision site for cesarean delivery is important in infection prevention
Dr. Barbieri’s editorial very nicely explained strategies to reduce the risk of post–cesarean delivery surgical site infection (SSI). However, what was not mentioned, in my opinion, is the most important preventive strategy. Selecting the site for the initial skin incision plays a great role in whether or not the patient will develop an infection postoperatively.
Pfannenstiel incisions are popular because of their obvious cosmetic benefit. In nonemergent cesarean deliveries, most ObGyns try to use this incision. However, exactly where the incision is placed plays a large role in the genesis of a postoperative wound infection. The worst place for such incisions is in the crease above the pubis and below the panniculus. Invariably, this area remains moist and macerated, especially in obese patients, thus providing a fertile breeding ground for bacteria. This problem can be avoided by incising the skin approximately 2 cm cranial to and parallel to the aforementioned crease, provided that the panniculus is not too large. The point is that the incision should be placed in an area where it has a chance to stay dry.
Sometimes patients who are hugely obese require great creativity in the placement of their transverse skin incision. I recall one patient, pregnant with triplets, whose abdomen was so large that her umbilicus was over the region of the lower uterine segment when she was supine on the operating room table. Some would have lifted up her immense panniculus and placed the incision in the usual crease site. This would be problematic for obtaining adequate exposure to deliver the babies, and the risk of developing an incisional infection would be very high. Therefore, a transverse incision was made just below her umbilicus. The panniculus was a nonissue regarding gaining adequate exposure and, when closed, the incision remained completely dry and uninfected. The patient did extremely well postoperatively and had no infectious sequelae.
David L. Zisow, MD
Baltimore, Maryland
Extraperitoneal approach should be considered
I enjoyed the editorial on reducing surgical site infection, especially the references to the historical Halsted principles of surgery. “He was the first in this country to promulgate the philosophy of ‘safe’ surgery.”1 Regarding surgical principles of cesarean delivery, the pioneering German obstetricians in the 1930s were keenly aware that avoiding the peritoneal cavity was instrumental in reducing morbidity and mortality. They championed the safety of the extraperitoneal approach as the fundamental principle of cesarean delivery for maternal safety.2
I learned to embrace the principles of Kaboth while learning the technique in 1968–1972. Thus, for more than 30 years, I used the extraperitoneal approach to access the lower uterine segment, avoiding entrance into the abdominal cavity. My patients seemed to benefit. As the surgeon, I also benefited: with short operative delivery times, less postoperative pain and minor morbidities, fewer phone calls from nursing staff, and less difficulty for my patients. I had not contaminated the peritoneal cavity and avoided all those inherent problems. The decision to open the peritoneal cavity has not been subjected to the rigors of critical analysis.3 I think that Kaboth’s principles remain worthy of consideration even today.
Contemporary experiences in large populations such as in India and China that use the extraperitoneal cesarean approach seem to implicitly support Kaboth’s principles. However, in the milieu of evidence-based medicine, extraperitoneal cesarean delivery has not been adequately studied.4 Just maybe the extraperitoneal approach should be considered and understood as a primary surgical technique for cesarean deliveries; just maybe it deserves a historical asterisk alongside the Halsted dicta.
Hedric Hanson, MD
Anchorage, Alaska
Dr. Barbieri responds
I thank Drs. Zisow and Hanson for their great recommendations and clinical pearls. I agree with Dr. Zisow that I should have mentioned the importance of optimal placement of the transverse skin incision. Incision in a skin crease that is perpetually moist increases the risk for a postoperative complication. When the abdomen is prepped for surgery, the skin crease above the pubis appears to be very inviting for placement of the skin incision. Dr. Hanson highlights the important option of an extraperitoneal approach to cesarean delivery. I have not thought about using this approach since the mid-1980s. Dr. Hanson’s recommendation that a randomized trial be performed comparing the SSI rate and other outcomes for extraperitoneal and intraperitoneal cesarean delivery is a great idea.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Cameron JL. William Steward Halsted: our surgical heritage. Ann Surg. 1997;225(5):445–458.
- Kaboth G. Die Technik des extraperitonealen Entibindungschnittes. Zentralblatt fur Gynakologie.1934;58(6):310–311.
- Berghella V, Baxter JK Chauhan SP. Evidence-based surgery for cesarean section. Am J Obstet Gynecol. 2005;193(5):1607–1617.
- Hofmeyr GJ, Mathai M, Shah AN, Novikova N. Techniques for caesarean section. Cochrane Database Syst Rev. 2008; CD004662.
- Cameron JL. William Steward Halsted: our surgical heritage. Ann Surg. 1997;225(5):445–458.
- Kaboth G. Die Technik des extraperitonealen Entibindungschnittes. Zentralblatt fur Gynakologie.1934;58(6):310–311.
- Berghella V, Baxter JK Chauhan SP. Evidence-based surgery for cesarean section. Am J Obstet Gynecol. 2005;193(5):1607–1617.
- Hofmeyr GJ, Mathai M, Shah AN, Novikova N. Techniques for caesarean section. Cochrane Database Syst Rev. 2008; CD004662.
Skip the catheter-directed thrombolytics
Background: Nearly half of all patients with proximal deep vein thrombosis (DVT) will develop postthrombotic syndrome at 2 years. Small trials have shown that the combination of catheter-directed delivery of thrombolytics, along with active mechanical clot removal, may prevent the postthrombotic syndrome.
Study design: Randomized, controlled trial.
Setting: Fifty-six clinical centers throughout the United States.
Synopsis: A total of 692 patients with symptomatic proximal DVT were randomized to receive either pharmacomechanical thrombolysis followed by anticoagulation or solely anticoagulation consistent with published guidelines. The primary outcome measured was the development of postthrombotic syndrome between 6 and 24 months. Over the 24 months that these patients were followed, 157 of 336 patients (47%) in the pharmacomechanical thrombolysis group and 171 of 355 patients (48%) in the control group developed postthrombotic syndrome (risk ratio, 0.96; 95% confidence interval, 0.82-1.11; P = .56). This result was consistent across predetermined subgroups.
Importantly, major bleeding within 10 days was more frequent in the pharmacomechanical thrombolysis group occurring in 6 of 336 patients (1.7%) versus 1 of 335 patients (0.3%) in the control group (P = .049). There was no significant difference in either recurrent venous thromboembolism at 24 months (12% in treatment group vs. 8% in control; P = .09) or deaths.
Of the 80 patients that did not present for follow-up postthrombotic syndrome assessments, two-thirds were in the control group, potentially leading to an underestimation of the effect of the intervention.
Bottom line: Pharmacomechanical catheter-directed thrombolysis does not reduce postthrombotic syndrome in proximal DVT and leads to an increased risk of major bleeding.
Citation: Vedantham S et al. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med. 2017 Dec 7;377(23):2240-52.
Dr. Scaletta is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.
Background: Nearly half of all patients with proximal deep vein thrombosis (DVT) will develop postthrombotic syndrome at 2 years. Small trials have shown that the combination of catheter-directed delivery of thrombolytics, along with active mechanical clot removal, may prevent the postthrombotic syndrome.
Study design: Randomized, controlled trial.
Setting: Fifty-six clinical centers throughout the United States.
Synopsis: A total of 692 patients with symptomatic proximal DVT were randomized to receive either pharmacomechanical thrombolysis followed by anticoagulation or solely anticoagulation consistent with published guidelines. The primary outcome measured was the development of postthrombotic syndrome between 6 and 24 months. Over the 24 months that these patients were followed, 157 of 336 patients (47%) in the pharmacomechanical thrombolysis group and 171 of 355 patients (48%) in the control group developed postthrombotic syndrome (risk ratio, 0.96; 95% confidence interval, 0.82-1.11; P = .56). This result was consistent across predetermined subgroups.
Importantly, major bleeding within 10 days was more frequent in the pharmacomechanical thrombolysis group occurring in 6 of 336 patients (1.7%) versus 1 of 335 patients (0.3%) in the control group (P = .049). There was no significant difference in either recurrent venous thromboembolism at 24 months (12% in treatment group vs. 8% in control; P = .09) or deaths.
Of the 80 patients that did not present for follow-up postthrombotic syndrome assessments, two-thirds were in the control group, potentially leading to an underestimation of the effect of the intervention.
Bottom line: Pharmacomechanical catheter-directed thrombolysis does not reduce postthrombotic syndrome in proximal DVT and leads to an increased risk of major bleeding.
Citation: Vedantham S et al. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med. 2017 Dec 7;377(23):2240-52.
Dr. Scaletta is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.
Background: Nearly half of all patients with proximal deep vein thrombosis (DVT) will develop postthrombotic syndrome at 2 years. Small trials have shown that the combination of catheter-directed delivery of thrombolytics, along with active mechanical clot removal, may prevent the postthrombotic syndrome.
Study design: Randomized, controlled trial.
Setting: Fifty-six clinical centers throughout the United States.
Synopsis: A total of 692 patients with symptomatic proximal DVT were randomized to receive either pharmacomechanical thrombolysis followed by anticoagulation or solely anticoagulation consistent with published guidelines. The primary outcome measured was the development of postthrombotic syndrome between 6 and 24 months. Over the 24 months that these patients were followed, 157 of 336 patients (47%) in the pharmacomechanical thrombolysis group and 171 of 355 patients (48%) in the control group developed postthrombotic syndrome (risk ratio, 0.96; 95% confidence interval, 0.82-1.11; P = .56). This result was consistent across predetermined subgroups.
Importantly, major bleeding within 10 days was more frequent in the pharmacomechanical thrombolysis group occurring in 6 of 336 patients (1.7%) versus 1 of 335 patients (0.3%) in the control group (P = .049). There was no significant difference in either recurrent venous thromboembolism at 24 months (12% in treatment group vs. 8% in control; P = .09) or deaths.
Of the 80 patients that did not present for follow-up postthrombotic syndrome assessments, two-thirds were in the control group, potentially leading to an underestimation of the effect of the intervention.
Bottom line: Pharmacomechanical catheter-directed thrombolysis does not reduce postthrombotic syndrome in proximal DVT and leads to an increased risk of major bleeding.
Citation: Vedantham S et al. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med. 2017 Dec 7;377(23):2240-52.
Dr. Scaletta is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.
Use of Short Peripheral Intravenous Catheters: Characteristics, Management, and Outcomes Worldwide
The majority of hospitalized patients worldwide have at least one peripheral intravenous catheter (PIVC),1 making PIVC insertion one of the most common clinical procedures. In the United States, physicians, advanced practitioners, and nurses insert over 300 million of these devices in hospitalized patients annually.2 Despite their prevalence, PIVCs are associated with high rates of complications, including insertion difficulty, phlebitis, infiltration, occlusion, dislodgment, and catheter-associated bloodstream infection (CABSI), known to increase morbidity and mortality risk.2-9 Up to 90% of PIVCs are prematurely removed owing to failure before planned replacement or before intravenous (IV) therapy completion.3-6,10-12
PIVC complication and failure commonly triggers insertion of a replacement device and can entail significant costs.2-4 One example is PIVC-related CABSI, where treatment costs have been estimated to be between US$35,000 and US$56,000 per patient.6,13 Another important consideration is the pain and anxiety experienced by patients who need a replacement device, particularly those with difficult vascular access, who may require multiple cannulation attempts to replace a PIVC.12,14-16 In developing nations, serious adverse events related to PIVCs are even more concerning, because hospital acquired infection rates and associated mortality are nearly 20 times greater than in developed nations.17
A number of evidence-based interventions have been suggested to reduce PIVC failure rates. In addition to optimal hand hygiene when inserting or accessing a PIVC to prevent infection,18 recommended interventions include placement of the PIVC in an area of non-flexion such as the forearm to provide stability for the device and to reduce patient discomfort, securing the PIVC to reduce movement of the catheter at the insertion site and within the blood vessel, and use of occlusive dressings that reduce the risk of external contamination of the PIVC site.11,19,20 Best practice guidelines also recommend the prompt removal of devices that are symptomatic (when phlebitis or other complications are suspected) and when the catheter is no longer required.21,22
Recent evidence has demonstrated that catheter size can have an impact on device survival rates. In adults, large-bore catheters of 18 gauge (G) or higher were found to have an increased rate of thrombosis, and smaller-bore catheters of 22G or lower (in adults) were found to have higher rates of dislodgment and occlusion/infiltration. The catheter size recommended for adults based on the latest evidence for most clinical applications is 20G.3,20,23,24 In addition, the documentation of insertion, maintenance, and removal of PIVCs in the medical record is a requirement in most healthcare facilities worldwide and is recommended by best practice guidelines; however, adherence remains a challenge.1,19
The concerning prevalence of PIVC-related complications and the lack of comparative data internationally on organizational compliance with best practice guidelines formed the rationale for this study. Our study aim was to describe the insertion characteristics, management practices, and outcomes of PIVCs internationally and to compare these variables to recommended best practice.
MATERIALS AND METHODS
Study Design and Participants
In this international cross-sectional study, we recruited hospitals through professional networks, including vascular access, infection prevention, safety and quality, nursing, and hospital associations (Appendix 2). Healthcare organizations, government health departments, and intravascular device suppliers were informed of the study and requested to further disseminate information through their networks. A study website was developed,25 and social media outlets, including Twitter®, LinkedIn®, and Facebook®, were used to promote the study.
Approval was granted by the Griffith University Human Research Ethics Committee in Australia (reference number NRS/34/13/HREC). In addition, evidence of study site and local institutional review board/ethics committee approval was required prior to study commencement. Each participating site agreed to follow the study protocol and signed an authorship agreement form. No financial support was provided to any site.
Hospitalized adult and pediatric patients with a PIVC in situ on the day of the study were eligible for inclusion. Sample size was determined by local capacity. Hospitals were encouraged to audit their entire institution if possible; however, data were accepted from as little as one ward. Data collectors comprised nurses and doctors with experience in PIVC assessment. They were briefed on the study protocol and data collection forms by the local site coordinator, and they were supported by an overall global coordinator. Clinicians assessed the PIVC insertion site and accessed hospital records to collect data related to PIVC insertion, concurrent medications, and IV fluid orders. Further clarification of data was obtained if necessary by the clinicians from the patients and treating staff. No identifiable patient information was collected.
Data Collection
To assess whether clinical facilities were following best practice recommendations, the study team developed three data collection forms to collect information regarding site characteristics (site questionnaire), track participant recruitment (screening log), and collect data regarding PIVC characteristics and management practices (case report form [CRF]). All forms were internally and externally validated following a pilot study involving 14 sites in 13 countries.1
The CRF included variables used to assess best practice interventions, such as catheter insertion characteristics (date and time, reason, location, profession of inserter, anatomical site of placement), catheter type (gauge, brand, and product), insertion site assessment (adverse symptoms, dressing type and integrity), and information related to the IV therapy (types of IV fluids and medications, flushing solutions). Idle PIVCs were defined as not being used for blood sampling or IV therapy in the preceding 24 h.
Data collection forms were translated into 15 languages by professional translators and back-translated for validity. Translation of some languages included additional rigor. For example, Spanish-speaking members from the Spanish mainland as well as from South America were employed so that appropriate synonyms were used to capture local terms and practice. Three options were provided for data entry: directly into a purpose-developed electronic database (Lime Survey® Project, Hamburg, Germany); on paper, then transcribed into the survey database at a later time by the hospital site; or paper entry then sent (via email or post) to the coordinating center for data entry. Once cleaned and collated, all data were provided to each participating hospital to confirm accuracy and for site use in local quality improvement processes. Data were collected between June 1, 2014 and July 31, 2015.
Statistical Analysis
All data management was undertaken using SAS statistical software (SAS Institute Inc., Cary NC, USA). Results are presented for eight geographical regions using descriptive statistics (frequencies, percentages, and 95% CIs) for the variables of interest. To assess trends in catheter dwell time and rates of phlebitis, Poisson regression was used. All analyses were undertaken using the R language for statistical analysis (R Core Team, Vienna, Austria). The (STROBE (Strengthening the Reporting of Observational Studies in Epidemiology statement) guidelines for cross-sectional studies were followed, and results are presented according to these recommendations.26
RESULTS
Of the 415 hospitals that participated in this study, 406 had patients with PIVCs on the day of the study (the others being small rural centers). Thus, a total of 40,620 PIVCs in 38,161 patients from 406 hospitals in 51 countries were assessed, with no more than 5% missing data for any CRF question. There were 2459 patients (6.1%) with two or more PIVCs concurrently in situ. The median patient age was 59 y (interquartile range [IQR], 37–74 y), and just over half were male (n = 20,550, 51%). Hospital size ranged from fewer than 10 beds to over 1,000 beds, and hospitals were located in rural, regional, and metropolitan districts. The majority of countries (n = 31, 61%) contributed multiple sites, the highest being Australia with 79 hospitals. Countries with the most PIVCs studied were Spain (n = 5,553, 14%) and the United States (n = 5,048, 12%).
General surgical (n = 15,616, 39%) and medical (n = 15,448, 38%) patients represented most of the population observed. PIVCs were inserted primarily in general wards or clinics (n = 22,167, 55%) or in emergency departments (n = 7,388, 18%; Table) and for the administration of IV medication (n = 28,571, 70%) and IV fluids (n = 7,093, 18%; Table).
Globally, nurses were the primary PIVC inserters (n = 28,575, 71%); however, Australia/New Zealand had only 26% (n = 1,518) of PIVCs inserted by this group (Table). Only about one-third of PIVCs were placed in an area of non-flexion (forearm, n = 12,675, 31%, Table) the majority (n = 27,856, 69%) were placed in non-recommended anatomical sites (Figure 1). Most PIVCs were placed in the hand (n = 13,265, 32.7%) followed by the antecubital veins (n = 6176, 15.2%) and the wrist (n = 5,465, 13.5%). Site selection varied widely across the regions; 29% (n = 1686) of PIVCs in Australia/New Zealand were inserted into the antecubital veins, twice the study group average. Over half of the PIVCs inserted in the Middle East were placed in the hand (n = 295, 56%). This region also had the highest prevalence of devices placed in nonrecommended sites (n = 416, 79%; Figure 1).
The majority of PIVCs (n = 27,192, 67%; Table) were of recommended size (20–22G); however, some devices were observed to be large (14–18G; n = 6,802, 17%) or small (24-26g; n = 4,869, 12%) in adults. In Asia, 41% (n = 2,617) of devices inserted were 24-26G, more than three times the global rate. Half of all devices in Asia (n = 3,077, 48%) and the South Pacific (n = 67, 52%) were of a size not recommended for routine IV therapy (Figure 2).
The primary dressing material used was a transparent dressing (n = 31,596, 77.8%; Table); however, nearly 1 in 5 dressings used had either nonsterile tape alone (n = 5,169, 13%; Appendix 4), or a sterile gauze and tape (n = 2,592, 6%; Appendix 4.1). We found a wide variation in the use of nonsterile tape, including 1 in every 3 devices in South America dressed with nonsterile tape (n = 714, 30%) and a larger proportion in Africa (n = 543, 19%) and Europe (n = 3,056, 18%). Nonsterile tape was rarely used in North America and Australia/New Zealand. Although most PIVC dressings were clean, dry, and intact (n = 31,786, 79%; Table), one-fifth overall were compromised (moist, soiled, and/or lifting off the skin). Compromised dressings (Appendix 4.2) were more prevalent in Australia/New Zealand (n = 1,448; 25%) and in Africa (n = 707, 25%) than elsewhere.
Ten percent of PIVCs (n = 4,204) had signs and/or symptoms suggestive of phlebitis (characterized by pain, redness and/or swelling at the insertion site; Appendix 4.3). The highest prevalence of phlebitis occurred in Asia (n = 1,021, 16%), Africa (n = 360, 13%), and South America (n = 284, 12%). Pain and/or redness were the most common phlebitis symptoms. We found no association between dwell time of PIVCs and phlebitis rates (P = .085). Phlebitis rates were 12% (Days 1-3; n = 15,625), 16% (Days 4-7; n = 3,348), 10% (Days 8-21; n = 457), and 13% (Day21+; n = 174). Nearly 10% (n = 3,879) of catheters were observed to have signs of malfunction such as blood in the infusion tubing, leaking at the insertion site, or dislodgment (Appendix 4.4).
We observed 14% (n = 5,796) of PIVCs to be idle (Appendix 4.5), defined as not used in the preceding 24 h. Nearly one-fourth of all devices in North America (n = 1,230, 23%) and Australia/New Zealand (n = 1,335, 23%) were idle. PIVC documentation in hospital records was also poor, nearly half of all PIVCs (n = 19,768, 49%) had no documented date and time of insertion. The poorest compliance was in Australia/New Zealand (n = 3,428, 59%; Appendix 4.6). We also observed that 1 in 10 PIVCs had no documentation regarding who inserted the PIVC (n = 3,905). Thirty-six percent of PIVCs (n = 14,787) had no documented assessment of the PIVC site on the day of review (Appendix 4.7), including over half of all PIVCs in Asia (n = 3,364, 52%). Overall, the median dwell at the time of assessment for PIVCs with insertion date/time documented was 1.5 d (IQR, 1.0–2.5 d).
DISCUSSION
This international assessment of more than 40,000 PIVCs in 51 countries provides great insight into device characteristics and variation in management practices. Predominantly, PIVCs were inserted by nurses in the general ward environment for IV medication. One in ten PIVCs had at least one symptom of phlebitis, one in ten were dysfunctional, one in five PIVC dressings were compromised, and one in six PIVCs had not been used in the preceding 24 h. Nearly half of the PIVCs audited had the insertion date and time missing.
Regional variation was found in the professions inserting PIVCs, as well as in anatomical placement. In Australia/New Zealand, the proportion of nurses inserting PIVCs was much lower than the study group average (26% vs 71%). Because these countries contributed a substantial number of hospitals to the study, this seems a representative finding and suggests a need for education targeted at nurses for PIVC insertion in this region. The veins in the forearm are recommended as optimal for PIVC insertion in adults, rather than areas of high flexion, because the forearm provides a wide surface area to secure and dress PIVCs. Forearm placement can reduce pain during catheter dwell as well as decrease the risk of accidental removal or occlusion.3,19,27 We found only one-third of PIVCs were placed in the forearm, with most placed in the hand, antecubital veins, or wrist. This highlights an inconsistency with published recommendations and suggests that additional training and technology are required so that staff can better identify and insert PIVCs in the forearm for other than very short-term (procedural) PIVCp;s.19
Phlebitis triggering PIVC failure remains a global clinical challenge with numerous phlebitis definitions and varied assessment techniques.10 The prevalence of phlebitis has been difficult to approximate with varying estimates and definitions in the literature; however, it remains a key predictor of PIVC failure.6,10 Identification of this complication and prompt removal of the device is critical for patient comfort and reducing CABSI risk.5,28 The overall prevalence of phlebitis signs or symptoms (defined in this study as having one or more signs of redness, swelling, or pain surrounding the insertion site) was just over 10%, with pain and/or redness being most prevalent. These compromised PIVCs had not been removed as is recommended for such complications.19,28 Considering that our study was a snapshot at only one time point, the per-catheter incidence of phlebitis would be even higher; interestingly, among PIVCs with a documented insertion date and time, we observed that dwell time did not influence phlebitis rates.
Another concern is that nearly 10% (n = 3,879) of PIVCs were malfunctioning (eg, leaking) but were still in place. To bring these problems into context, around 2 billion PIVCs are used annually worldwide; as a consequence, millions of patients suffer from painful or malfunctioning PIVCs staff had not responded.1,29 The placement of large-bore catheters, and smaller-gauge ones in adults, is known to increase the incidence of malfunction that leads to failure. There are a number of sound clinical reasons for the use of large-bore (eg, resuscitation and rapid fluid replacement) or small-bore (eg, difficult venous access with small superficial veins only visible and palpable) catheters. However, it would be expected that only a small proportion of patients would require these devices, and not one in three devices as we identified. This finding suggests that some PIVCs were inappropriate in size for general IV therapy and may reflect antiquated hospital policies for some clinical cohorts.30,31
Overall, transparent dressings were used to cover the PIVC, but a number of patients were observed to have a sterile gauze and tape dressing (n = 2,592, 6%). Although the latter is less common, both dressing approaches are recommended in clinical practice guidelines because there is a lack of high-quality evidence regarding which is superior.21,22,32 Of concern was the use of nonsterile tape to dress the PIVC (n = 5,169, 12.7%). We found the prevalence of nonsterile tape use to be higher in lower-resourced countries in South America (n = 714, 30%), Africa (n = 543, 19%) and Europe (n = 3,056, 18%) and this was likely related to institutional cost reduction practices.
This finding illustrates an important issue regarding proper PIVC care and management practices in developing nations. It is widely known that access to safe health care in lower-resourced nations is challenging and that rates of mortality related to healthcare-associated infections are much higher. Thus, the differences we found in PIVC management practices in these countries are not surprising.33,34 International health networks such as the Infection Control Africa Network, the International Federation of Infection Control, and the Centers for Disease Control and Prevention can have great influence on ministries of health and clinicians in these countries to develop coordinated efforts for safe and sustainable IV practices to reduce the burden of hospital-acquired infections and related morbidity and mortality.
We found that 14% of all PIVCs had no documented IV medication or IV fluid administered in the previous 24 h, strongly indicating that they were no longer needed. Australia/New Zealand, Europe, and North America were observed to have a higher prevalence of idle catheters than the remaining regions. This suggests that an opportunity exists to develop surveillance systems that better identify idle devices for prompt removal to reduce infection risk and patient discomfort. Several randomized controlled trials, a Cochrane review, and clinical practice guidelines recommend prompt removal of PIVCs when not required, if there are any complications, or if the PIVC was inserted urgently without an aseptic insertion technique.21,28,35,36 Idle PIVCs have been implicated in adverse patient outcomes, including phlebitis and CABSI.13,27
The substantial proportion of patients with a PIVC in this study who had no clinical indication for a PIVC, a symptomatic insertion site, malfunctioning catheter, and suboptimal dressing quality suggests the need for physicians, advanced practitioners, and nurses to adopt evidence-based PIVC insertion and maintenance bundles and supporting checklists to reduce the prevalence of PIVC complications.19,21,38-40 Recommended strategies for inclusion in PIVC maintenance bundles are prompt removal of symptomatic and/or idle catheters, hand hygiene prior to accessing the catheter, regular assessment of the device, and replacement of suboptimal dressings.41,42 This approach should be implemented across all clinical specialties involved in PIVC insertion and care.
Our study findings need to be considered within the context of some limitations. The cross-sectional design prevented follow-up of PIVCs until removal to collect outcomes, including subsequent PIVC complications and/or failure, following the study observation. Ideally, data collection could have included patient-level preferences for PIVC insertion, history of PIVC use and/or failure, the number of PIVC insertion attempts, and the number of PIVCs used during that hospitalization. However, a cohort study of this magnitude was not feasible, particularly because all sites contributed staff time to complete the data collection. Only half of all initially registered sites eventually participated in the study; reasons for not participating were cited as local workload constraints and/or difficulties in applying for local approvals. Although efforts to enroll hospitals worldwide were exhaustive, our sample was not randomly selected but relied on self-selection and so is not representative, particularly for countries that contributed only one hospital site. Caution is also required when comparing inter regional differences, particularly developing regions, because better-resourced/academic sites were possibly over represented in the sample. Nevertheless, PIVC variables differed significantly between participating hospitals, suggesting that the data represent a reasonable reflection of hospital variability.
CONCLUSIONS
On the basis of this international investigation, we report variations in the characteristics, management practices, and outcomes of PIVCs inserted in hospital patients from 51 countries. Many PIVCs were idle, symptomatic, had substandard dressings, and were inserted in suboptimal anatomical sites. Despite international best practice guidelines, a large number of patients had PIVCs that were already failing or at risk of complications, including infection. A stronger focus is needed on compliance with PIVC insertion and management guidelines; better surveillance of PIVC sites; and improved assessment, decision-making, and documentation.
Acknowledgements
We are extremely grateful to colleagues from across the globe who committed their time and effort to this study (for full details of countries and team members see Appendix 1).
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2. Zingg W, Pittet D. Peripheral venous catheters: an under-evaluated problem. Int J Antimicrob Agents. 2009;34(suppl 4):S38-S42. https:/ doi.org/10.1016/S0924-8579(09)70565-5
3. Wallis MC, McGrail MR, Webster J, Gowardman JR, Playford G, Rickard CM. Risk factors for PIV catheter failure: a multivariate analysis from a randomized control trial. Infect. Control Hosp Epidemiol. 2014;35(1):63-68. https:/doi.org/10.1086/674398.
4. Pujol M, Hornero A, Saballs M, et al. Clinical epidemiology and outcomes of peripheral venous catheter-related bloodstream infections at a university-affiliated hospital. J Hosp Infect. 2007;67(1):22-29.
5. Fakih MG, Jones K, Rey JE, et al. Sustained improvements in peripheral venous catheter care in non–intensive care units: a quasi-experimental controlled study of education and feedback. Infect. Control Hosp Epidemiol. 2012;33(5):449-455. https:/doi.org/10.1086/665322.
6. Helm RE, Klausner JD, Klemperer JD, Flint LM, Huang E. Accepted but unacceptable: peripheral IV catheter failure. J Infus Nurs. 2015;38(3):189-203. https:/ doi.org/10.1097/NAN.0000000000000100.
7. Austin ED, Sullivan SB, Whittier S, Lowy FD, Uhlemann AC. Peripheral intravenous catheter placement is an underrecognized source of Staphylococcus aureus bloodstream infection. Open Forum Infect Dis. 2016;3(2):ofw072. https:/ doi.org/10.1093/ofid/ofw072.
8. Stuart RL, Cameron D, Scott C, et al. Peripheral intravenous catheter-associated Staphylococcus aureus bacteraemia: more than 5 years of prospective data from two tertiary health services. Med J Aust. 2013;198(10):551-553.
9. Trinh TT, Chan PA, Edwards O, et al. Peripheral venous catheter-related Staphylococcus aureus bacteremia. Infect Control Hosp Epidemiol. 2011;32(6):579-583. https:/doi.org/10.1086/660099.
10. Ray Barruel G, Polit DF, Murfield JE, Rickard CM. Infusion phlebitis assessment measures: a systematic review. J Eval Clin Pract. 2014;20(2):191-202. https:/ doi.org/ 10.1111/jep.12107
11. Marsh N, Webster J, Flynn J, et al. Securement methods for peripheral venous catheters to prevent failure: a randomised controlled pilot trial. J Vasc Access. 2015;16(3):237-244. https:/doi.org /10.5301/jva.5000348.
12. Carr PJ, Higgins NS, Cooke ML, Rippey J, Rickard CM. Tools, clinical prediction rules, and algorithms for the insertion of peripheral intravenous catheters in adult hospitalized patients: a systematic scoping review of literature. J Hosp Med. 2017;12(10):851-858. https:/doi.org/ 10.12788/jhm.2836
13. Becerra MB, Shirley D, Safdar N. Prevalence, risk factors, and outcomes of idle intravenous catheters: An integrative review. Am J Infect Control. 2016;44(10):e167-e172. https:/ doi.org/10.1016/j.ajic.2016.03.073.
14. Robinson-Reilly M, Paliadelis P, Cruickshank M. Venous access: the patient experience. Support Care Cancer. 2016;24(3):1181-1187. https:/ doi.org/10.1007/s00520-015-2900-9.
15. Petroski A, Frisch A, Joseph N, Carlson JN. Predictors of difficult pediatric intravenous access in a community Emergency Department. J Vasc Access. 2015;16(6):521-526. https:/doi.org/10.5301/jva.5000411
16. Sou V, McManus C, Mifflin N, Frost SA, Ale J, Alexandrou E. A clinical pathway for the management of difficult venous access. BMC Nurs. 2017;16(1):64. https:/ doi.org/10.1186/s12912-017-0261-z
17. World Health Organization. Report on the burden of endemic health care-associated infection worldwide. Geneva2011. 9241501502.
18. Hirschmann H, Fux L, Podusel J, et al. The influence of hand hygiene prior to insertion of peripheral venous catheters on the frequency of complications. J Hosp Infect. 2001;49(3):199-203. https:/doi.org/10.1053/jhin.2001.1077
19. Gorski L, Hadaway L, Hagle M, McGoldrick M, Orr M, Doellman D. Infusion therapy standards of practice. J Infus Nurs. 2016;39(suppl 1):S1-S159.
20. Abolfotouh MA, Salam M, Bani-Mustafa Aa, White D, Balkhy HH. Prospective study of incidence and predictors of peripheral intravenous catheter-induced complications. Ther Clin Risk Manag. 2014;10:993. https://doi.org/10.2147/TCRM.S74685.
21. Loveday H, Wilson J, Pratt R, et al. epic3: national evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England. J Hosp Infect. 2014;86(suppl 1):S1-S70. https:/doi.org/10.1016/S0195-6701(13)60012-2.
22. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis. 2011;52(9):e162-e193. https:/doi.org/10.1093/cid/cir257
23. Cicolini G, Bonghi AP, Di Labio L, Di Mascio R. Position of peripheral venous cannulae and the incidence of thrombophlebitis: an observational study. J Adv Nurs. 2009;65(6):1268-1273. https:/doi.org/10.1111/j.1365-2648.2009.04980.x.
24. Marsh N, Webster J, Larson E, Cooke M, Mihala G, Rickard C. Observational study of peripheral intravenous catheter outcomes in adult hospitalized patients: a multivariable analysis of peripheral intravenous catheter failure. J Hosp Med. 2018;13(2):83-89. https:/doi.org/10.12788/jhm.2867.
25. One Million Global Catheters PIVC Worldwide Prevalence study. OMG study website http://www.omgpivc.org/. Accessed 23 March, 2017.
26. Von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg. 2014;12(12):1495-1499. https:/doi.org/ 10.1136/bmj.39335.541782.AD
27. Fields JM, Dean AJ, Todman RW, et al. The effect of vessel depth, diameter, and location on ultrasound-guided peripheral intravenous catheter longevity. Am J Emerg Med. 2012;30(7):1134-1140. https:/doi.org/10.1016/j.ajem.2011.07.027.
28. Patel SA, Alebich MM, Feldman LS. Choosing wisely: things we do for no reason. Routine replacement of peripheral intravenous catheters. J Hosp Med. 2017;12(1):42-45.
29. Newswire. Global Peripheral I.V. Catheter Market 2014 - 2018. New York, PR Newswire Assoc; 2014.
30. Webster J, Larsen E, Booker C, Laws J, Marsh N. Prophylactic insertion of large bore peripheral intravenous catheters in maternity patients for postpartum haemorrhage: A cohort study. Aust N Z J Obstet Gynaecol. 2017.https:/doi.org/10.1111/ajo.12759.
31. Rivera A, Strauss K, van Zundert A, Mortier E. Matching the peripheral intravenous catheter to the individual patient. Acta Anaesthesiol Belg. 2006;58(1):19.
32. Webster J, Gillies D, O’Riordan E, Sherriff KL, Rickard CM. Gauze and tape and transparent polyurethane dressings for central venous catheters. Cochrane Database Syst Rev. 2011;11:CD003827. https:/doi.org/10.1002/14651858.CD003827.pub2
33. Dieleman JL, Templin T, Sadat N, et al. National spending on health by source for 184 countries between 2013 and 2040. Lancet. 2016;387(10037):2521-2535. https:/ doi.org/10.1016/S0140-6736(16)30167-2.
34. Allegranzi B, Nejad SB, Combescure C, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet. 2011;377(9761):228-241. https:/ doi.org/10.1016/S0140-6736(10)61458-4.
35. Rickard CM, Webster J, Wallis MC, et al. Routine versus clinically indicated replacement of peripheral intravenous catheters: a randomised controlled equivalence trial. Lancet. 2012;380(9847):1066-1074. https:/doi.org/10.1016/S0140-6736(12)61082-4.
36. Webster J, Osborne S, Rickard CM, New K. Clinically indicated replacement versus routine replacement of peripheral venous catheters. Cochrane Database Syst Rev. 2015;8:CD007798. https://doi.org/10.1002/14651858.CD007798.pub4.
37. Yagnik L, Graves A, Thong K. Plastic in patient study: Prospective audit of adherence to peripheral intravenous cannula monitoring and documentation guidelines, with the aim of reducing future rates of intravenous cannula-related complications. Am J Infect Control. 2017;45(1):34-38. https:/doi.org/10.1016/j.ajic.2016.09.008.
38. Boyd S, Aggarwal I, Davey P, Logan M, Nathwani D. Peripheral intravenous catheters: the road to quality improvement and safer patient care. J Hosp Infect. 2011;77(1):37-41. https:/doi.org/10.1016/j.jhin.2010.09.011.
39. DeVries M, Valentine M, Mancos P. Protected clinical indication of peripheral intravenous lines: successful implementation. J Assoc Vasc Access. 2016;21(2):89-92. https://doi.org/10.1016/j.java.2016.03.001.
40. Rhodes D, Cheng A, McLellan S, et al. Reducing Staphylococcus aureus bloodstream infections associated with peripheral intravenous cannulae: successful implementation of a care bundle at a large Australian health service. J Hosp Infect. 2016;94(1):86-91. https:/doi.org/10.1016/j.jhin.2016.05.020.
41. Rinke ML, Chen AR, Bundy DG, et al. Implementation of a central line maintenance care bundle in hospitalized pediatric oncology patients. Pediatr. 2012;130(4):e996-e1004. https:/doi.org/10.1542/peds.2012-0295.
42. Marshall J, Mermel L, Fakih M, Hadaway L, Kallen A, O’Grady N. Strategies to prevent central line–associated bloodstream infections in acute care hospitals: 2014 update. Infect. Control Hosp Epidemiol. 2014;35(suppl 2):S89-107. https:/doi.org/10.1086/676533.
The majority of hospitalized patients worldwide have at least one peripheral intravenous catheter (PIVC),1 making PIVC insertion one of the most common clinical procedures. In the United States, physicians, advanced practitioners, and nurses insert over 300 million of these devices in hospitalized patients annually.2 Despite their prevalence, PIVCs are associated with high rates of complications, including insertion difficulty, phlebitis, infiltration, occlusion, dislodgment, and catheter-associated bloodstream infection (CABSI), known to increase morbidity and mortality risk.2-9 Up to 90% of PIVCs are prematurely removed owing to failure before planned replacement or before intravenous (IV) therapy completion.3-6,10-12
PIVC complication and failure commonly triggers insertion of a replacement device and can entail significant costs.2-4 One example is PIVC-related CABSI, where treatment costs have been estimated to be between US$35,000 and US$56,000 per patient.6,13 Another important consideration is the pain and anxiety experienced by patients who need a replacement device, particularly those with difficult vascular access, who may require multiple cannulation attempts to replace a PIVC.12,14-16 In developing nations, serious adverse events related to PIVCs are even more concerning, because hospital acquired infection rates and associated mortality are nearly 20 times greater than in developed nations.17
A number of evidence-based interventions have been suggested to reduce PIVC failure rates. In addition to optimal hand hygiene when inserting or accessing a PIVC to prevent infection,18 recommended interventions include placement of the PIVC in an area of non-flexion such as the forearm to provide stability for the device and to reduce patient discomfort, securing the PIVC to reduce movement of the catheter at the insertion site and within the blood vessel, and use of occlusive dressings that reduce the risk of external contamination of the PIVC site.11,19,20 Best practice guidelines also recommend the prompt removal of devices that are symptomatic (when phlebitis or other complications are suspected) and when the catheter is no longer required.21,22
Recent evidence has demonstrated that catheter size can have an impact on device survival rates. In adults, large-bore catheters of 18 gauge (G) or higher were found to have an increased rate of thrombosis, and smaller-bore catheters of 22G or lower (in adults) were found to have higher rates of dislodgment and occlusion/infiltration. The catheter size recommended for adults based on the latest evidence for most clinical applications is 20G.3,20,23,24 In addition, the documentation of insertion, maintenance, and removal of PIVCs in the medical record is a requirement in most healthcare facilities worldwide and is recommended by best practice guidelines; however, adherence remains a challenge.1,19
The concerning prevalence of PIVC-related complications and the lack of comparative data internationally on organizational compliance with best practice guidelines formed the rationale for this study. Our study aim was to describe the insertion characteristics, management practices, and outcomes of PIVCs internationally and to compare these variables to recommended best practice.
MATERIALS AND METHODS
Study Design and Participants
In this international cross-sectional study, we recruited hospitals through professional networks, including vascular access, infection prevention, safety and quality, nursing, and hospital associations (Appendix 2). Healthcare organizations, government health departments, and intravascular device suppliers were informed of the study and requested to further disseminate information through their networks. A study website was developed,25 and social media outlets, including Twitter®, LinkedIn®, and Facebook®, were used to promote the study.
Approval was granted by the Griffith University Human Research Ethics Committee in Australia (reference number NRS/34/13/HREC). In addition, evidence of study site and local institutional review board/ethics committee approval was required prior to study commencement. Each participating site agreed to follow the study protocol and signed an authorship agreement form. No financial support was provided to any site.
Hospitalized adult and pediatric patients with a PIVC in situ on the day of the study were eligible for inclusion. Sample size was determined by local capacity. Hospitals were encouraged to audit their entire institution if possible; however, data were accepted from as little as one ward. Data collectors comprised nurses and doctors with experience in PIVC assessment. They were briefed on the study protocol and data collection forms by the local site coordinator, and they were supported by an overall global coordinator. Clinicians assessed the PIVC insertion site and accessed hospital records to collect data related to PIVC insertion, concurrent medications, and IV fluid orders. Further clarification of data was obtained if necessary by the clinicians from the patients and treating staff. No identifiable patient information was collected.
Data Collection
To assess whether clinical facilities were following best practice recommendations, the study team developed three data collection forms to collect information regarding site characteristics (site questionnaire), track participant recruitment (screening log), and collect data regarding PIVC characteristics and management practices (case report form [CRF]). All forms were internally and externally validated following a pilot study involving 14 sites in 13 countries.1
The CRF included variables used to assess best practice interventions, such as catheter insertion characteristics (date and time, reason, location, profession of inserter, anatomical site of placement), catheter type (gauge, brand, and product), insertion site assessment (adverse symptoms, dressing type and integrity), and information related to the IV therapy (types of IV fluids and medications, flushing solutions). Idle PIVCs were defined as not being used for blood sampling or IV therapy in the preceding 24 h.
Data collection forms were translated into 15 languages by professional translators and back-translated for validity. Translation of some languages included additional rigor. For example, Spanish-speaking members from the Spanish mainland as well as from South America were employed so that appropriate synonyms were used to capture local terms and practice. Three options were provided for data entry: directly into a purpose-developed electronic database (Lime Survey® Project, Hamburg, Germany); on paper, then transcribed into the survey database at a later time by the hospital site; or paper entry then sent (via email or post) to the coordinating center for data entry. Once cleaned and collated, all data were provided to each participating hospital to confirm accuracy and for site use in local quality improvement processes. Data were collected between June 1, 2014 and July 31, 2015.
Statistical Analysis
All data management was undertaken using SAS statistical software (SAS Institute Inc., Cary NC, USA). Results are presented for eight geographical regions using descriptive statistics (frequencies, percentages, and 95% CIs) for the variables of interest. To assess trends in catheter dwell time and rates of phlebitis, Poisson regression was used. All analyses were undertaken using the R language for statistical analysis (R Core Team, Vienna, Austria). The (STROBE (Strengthening the Reporting of Observational Studies in Epidemiology statement) guidelines for cross-sectional studies were followed, and results are presented according to these recommendations.26
RESULTS
Of the 415 hospitals that participated in this study, 406 had patients with PIVCs on the day of the study (the others being small rural centers). Thus, a total of 40,620 PIVCs in 38,161 patients from 406 hospitals in 51 countries were assessed, with no more than 5% missing data for any CRF question. There were 2459 patients (6.1%) with two or more PIVCs concurrently in situ. The median patient age was 59 y (interquartile range [IQR], 37–74 y), and just over half were male (n = 20,550, 51%). Hospital size ranged from fewer than 10 beds to over 1,000 beds, and hospitals were located in rural, regional, and metropolitan districts. The majority of countries (n = 31, 61%) contributed multiple sites, the highest being Australia with 79 hospitals. Countries with the most PIVCs studied were Spain (n = 5,553, 14%) and the United States (n = 5,048, 12%).
General surgical (n = 15,616, 39%) and medical (n = 15,448, 38%) patients represented most of the population observed. PIVCs were inserted primarily in general wards or clinics (n = 22,167, 55%) or in emergency departments (n = 7,388, 18%; Table) and for the administration of IV medication (n = 28,571, 70%) and IV fluids (n = 7,093, 18%; Table).
Globally, nurses were the primary PIVC inserters (n = 28,575, 71%); however, Australia/New Zealand had only 26% (n = 1,518) of PIVCs inserted by this group (Table). Only about one-third of PIVCs were placed in an area of non-flexion (forearm, n = 12,675, 31%, Table) the majority (n = 27,856, 69%) were placed in non-recommended anatomical sites (Figure 1). Most PIVCs were placed in the hand (n = 13,265, 32.7%) followed by the antecubital veins (n = 6176, 15.2%) and the wrist (n = 5,465, 13.5%). Site selection varied widely across the regions; 29% (n = 1686) of PIVCs in Australia/New Zealand were inserted into the antecubital veins, twice the study group average. Over half of the PIVCs inserted in the Middle East were placed in the hand (n = 295, 56%). This region also had the highest prevalence of devices placed in nonrecommended sites (n = 416, 79%; Figure 1).
The majority of PIVCs (n = 27,192, 67%; Table) were of recommended size (20–22G); however, some devices were observed to be large (14–18G; n = 6,802, 17%) or small (24-26g; n = 4,869, 12%) in adults. In Asia, 41% (n = 2,617) of devices inserted were 24-26G, more than three times the global rate. Half of all devices in Asia (n = 3,077, 48%) and the South Pacific (n = 67, 52%) were of a size not recommended for routine IV therapy (Figure 2).
The primary dressing material used was a transparent dressing (n = 31,596, 77.8%; Table); however, nearly 1 in 5 dressings used had either nonsterile tape alone (n = 5,169, 13%; Appendix 4), or a sterile gauze and tape (n = 2,592, 6%; Appendix 4.1). We found a wide variation in the use of nonsterile tape, including 1 in every 3 devices in South America dressed with nonsterile tape (n = 714, 30%) and a larger proportion in Africa (n = 543, 19%) and Europe (n = 3,056, 18%). Nonsterile tape was rarely used in North America and Australia/New Zealand. Although most PIVC dressings were clean, dry, and intact (n = 31,786, 79%; Table), one-fifth overall were compromised (moist, soiled, and/or lifting off the skin). Compromised dressings (Appendix 4.2) were more prevalent in Australia/New Zealand (n = 1,448; 25%) and in Africa (n = 707, 25%) than elsewhere.
Ten percent of PIVCs (n = 4,204) had signs and/or symptoms suggestive of phlebitis (characterized by pain, redness and/or swelling at the insertion site; Appendix 4.3). The highest prevalence of phlebitis occurred in Asia (n = 1,021, 16%), Africa (n = 360, 13%), and South America (n = 284, 12%). Pain and/or redness were the most common phlebitis symptoms. We found no association between dwell time of PIVCs and phlebitis rates (P = .085). Phlebitis rates were 12% (Days 1-3; n = 15,625), 16% (Days 4-7; n = 3,348), 10% (Days 8-21; n = 457), and 13% (Day21+; n = 174). Nearly 10% (n = 3,879) of catheters were observed to have signs of malfunction such as blood in the infusion tubing, leaking at the insertion site, or dislodgment (Appendix 4.4).
We observed 14% (n = 5,796) of PIVCs to be idle (Appendix 4.5), defined as not used in the preceding 24 h. Nearly one-fourth of all devices in North America (n = 1,230, 23%) and Australia/New Zealand (n = 1,335, 23%) were idle. PIVC documentation in hospital records was also poor, nearly half of all PIVCs (n = 19,768, 49%) had no documented date and time of insertion. The poorest compliance was in Australia/New Zealand (n = 3,428, 59%; Appendix 4.6). We also observed that 1 in 10 PIVCs had no documentation regarding who inserted the PIVC (n = 3,905). Thirty-six percent of PIVCs (n = 14,787) had no documented assessment of the PIVC site on the day of review (Appendix 4.7), including over half of all PIVCs in Asia (n = 3,364, 52%). Overall, the median dwell at the time of assessment for PIVCs with insertion date/time documented was 1.5 d (IQR, 1.0–2.5 d).
DISCUSSION
This international assessment of more than 40,000 PIVCs in 51 countries provides great insight into device characteristics and variation in management practices. Predominantly, PIVCs were inserted by nurses in the general ward environment for IV medication. One in ten PIVCs had at least one symptom of phlebitis, one in ten were dysfunctional, one in five PIVC dressings were compromised, and one in six PIVCs had not been used in the preceding 24 h. Nearly half of the PIVCs audited had the insertion date and time missing.
Regional variation was found in the professions inserting PIVCs, as well as in anatomical placement. In Australia/New Zealand, the proportion of nurses inserting PIVCs was much lower than the study group average (26% vs 71%). Because these countries contributed a substantial number of hospitals to the study, this seems a representative finding and suggests a need for education targeted at nurses for PIVC insertion in this region. The veins in the forearm are recommended as optimal for PIVC insertion in adults, rather than areas of high flexion, because the forearm provides a wide surface area to secure and dress PIVCs. Forearm placement can reduce pain during catheter dwell as well as decrease the risk of accidental removal or occlusion.3,19,27 We found only one-third of PIVCs were placed in the forearm, with most placed in the hand, antecubital veins, or wrist. This highlights an inconsistency with published recommendations and suggests that additional training and technology are required so that staff can better identify and insert PIVCs in the forearm for other than very short-term (procedural) PIVCp;s.19
Phlebitis triggering PIVC failure remains a global clinical challenge with numerous phlebitis definitions and varied assessment techniques.10 The prevalence of phlebitis has been difficult to approximate with varying estimates and definitions in the literature; however, it remains a key predictor of PIVC failure.6,10 Identification of this complication and prompt removal of the device is critical for patient comfort and reducing CABSI risk.5,28 The overall prevalence of phlebitis signs or symptoms (defined in this study as having one or more signs of redness, swelling, or pain surrounding the insertion site) was just over 10%, with pain and/or redness being most prevalent. These compromised PIVCs had not been removed as is recommended for such complications.19,28 Considering that our study was a snapshot at only one time point, the per-catheter incidence of phlebitis would be even higher; interestingly, among PIVCs with a documented insertion date and time, we observed that dwell time did not influence phlebitis rates.
Another concern is that nearly 10% (n = 3,879) of PIVCs were malfunctioning (eg, leaking) but were still in place. To bring these problems into context, around 2 billion PIVCs are used annually worldwide; as a consequence, millions of patients suffer from painful or malfunctioning PIVCs staff had not responded.1,29 The placement of large-bore catheters, and smaller-gauge ones in adults, is known to increase the incidence of malfunction that leads to failure. There are a number of sound clinical reasons for the use of large-bore (eg, resuscitation and rapid fluid replacement) or small-bore (eg, difficult venous access with small superficial veins only visible and palpable) catheters. However, it would be expected that only a small proportion of patients would require these devices, and not one in three devices as we identified. This finding suggests that some PIVCs were inappropriate in size for general IV therapy and may reflect antiquated hospital policies for some clinical cohorts.30,31
Overall, transparent dressings were used to cover the PIVC, but a number of patients were observed to have a sterile gauze and tape dressing (n = 2,592, 6%). Although the latter is less common, both dressing approaches are recommended in clinical practice guidelines because there is a lack of high-quality evidence regarding which is superior.21,22,32 Of concern was the use of nonsterile tape to dress the PIVC (n = 5,169, 12.7%). We found the prevalence of nonsterile tape use to be higher in lower-resourced countries in South America (n = 714, 30%), Africa (n = 543, 19%) and Europe (n = 3,056, 18%) and this was likely related to institutional cost reduction practices.
This finding illustrates an important issue regarding proper PIVC care and management practices in developing nations. It is widely known that access to safe health care in lower-resourced nations is challenging and that rates of mortality related to healthcare-associated infections are much higher. Thus, the differences we found in PIVC management practices in these countries are not surprising.33,34 International health networks such as the Infection Control Africa Network, the International Federation of Infection Control, and the Centers for Disease Control and Prevention can have great influence on ministries of health and clinicians in these countries to develop coordinated efforts for safe and sustainable IV practices to reduce the burden of hospital-acquired infections and related morbidity and mortality.
We found that 14% of all PIVCs had no documented IV medication or IV fluid administered in the previous 24 h, strongly indicating that they were no longer needed. Australia/New Zealand, Europe, and North America were observed to have a higher prevalence of idle catheters than the remaining regions. This suggests that an opportunity exists to develop surveillance systems that better identify idle devices for prompt removal to reduce infection risk and patient discomfort. Several randomized controlled trials, a Cochrane review, and clinical practice guidelines recommend prompt removal of PIVCs when not required, if there are any complications, or if the PIVC was inserted urgently without an aseptic insertion technique.21,28,35,36 Idle PIVCs have been implicated in adverse patient outcomes, including phlebitis and CABSI.13,27
The substantial proportion of patients with a PIVC in this study who had no clinical indication for a PIVC, a symptomatic insertion site, malfunctioning catheter, and suboptimal dressing quality suggests the need for physicians, advanced practitioners, and nurses to adopt evidence-based PIVC insertion and maintenance bundles and supporting checklists to reduce the prevalence of PIVC complications.19,21,38-40 Recommended strategies for inclusion in PIVC maintenance bundles are prompt removal of symptomatic and/or idle catheters, hand hygiene prior to accessing the catheter, regular assessment of the device, and replacement of suboptimal dressings.41,42 This approach should be implemented across all clinical specialties involved in PIVC insertion and care.
Our study findings need to be considered within the context of some limitations. The cross-sectional design prevented follow-up of PIVCs until removal to collect outcomes, including subsequent PIVC complications and/or failure, following the study observation. Ideally, data collection could have included patient-level preferences for PIVC insertion, history of PIVC use and/or failure, the number of PIVC insertion attempts, and the number of PIVCs used during that hospitalization. However, a cohort study of this magnitude was not feasible, particularly because all sites contributed staff time to complete the data collection. Only half of all initially registered sites eventually participated in the study; reasons for not participating were cited as local workload constraints and/or difficulties in applying for local approvals. Although efforts to enroll hospitals worldwide were exhaustive, our sample was not randomly selected but relied on self-selection and so is not representative, particularly for countries that contributed only one hospital site. Caution is also required when comparing inter regional differences, particularly developing regions, because better-resourced/academic sites were possibly over represented in the sample. Nevertheless, PIVC variables differed significantly between participating hospitals, suggesting that the data represent a reasonable reflection of hospital variability.
CONCLUSIONS
On the basis of this international investigation, we report variations in the characteristics, management practices, and outcomes of PIVCs inserted in hospital patients from 51 countries. Many PIVCs were idle, symptomatic, had substandard dressings, and were inserted in suboptimal anatomical sites. Despite international best practice guidelines, a large number of patients had PIVCs that were already failing or at risk of complications, including infection. A stronger focus is needed on compliance with PIVC insertion and management guidelines; better surveillance of PIVC sites; and improved assessment, decision-making, and documentation.
Acknowledgements
We are extremely grateful to colleagues from across the globe who committed their time and effort to this study (for full details of countries and team members see Appendix 1).
The majority of hospitalized patients worldwide have at least one peripheral intravenous catheter (PIVC),1 making PIVC insertion one of the most common clinical procedures. In the United States, physicians, advanced practitioners, and nurses insert over 300 million of these devices in hospitalized patients annually.2 Despite their prevalence, PIVCs are associated with high rates of complications, including insertion difficulty, phlebitis, infiltration, occlusion, dislodgment, and catheter-associated bloodstream infection (CABSI), known to increase morbidity and mortality risk.2-9 Up to 90% of PIVCs are prematurely removed owing to failure before planned replacement or before intravenous (IV) therapy completion.3-6,10-12
PIVC complication and failure commonly triggers insertion of a replacement device and can entail significant costs.2-4 One example is PIVC-related CABSI, where treatment costs have been estimated to be between US$35,000 and US$56,000 per patient.6,13 Another important consideration is the pain and anxiety experienced by patients who need a replacement device, particularly those with difficult vascular access, who may require multiple cannulation attempts to replace a PIVC.12,14-16 In developing nations, serious adverse events related to PIVCs are even more concerning, because hospital acquired infection rates and associated mortality are nearly 20 times greater than in developed nations.17
A number of evidence-based interventions have been suggested to reduce PIVC failure rates. In addition to optimal hand hygiene when inserting or accessing a PIVC to prevent infection,18 recommended interventions include placement of the PIVC in an area of non-flexion such as the forearm to provide stability for the device and to reduce patient discomfort, securing the PIVC to reduce movement of the catheter at the insertion site and within the blood vessel, and use of occlusive dressings that reduce the risk of external contamination of the PIVC site.11,19,20 Best practice guidelines also recommend the prompt removal of devices that are symptomatic (when phlebitis or other complications are suspected) and when the catheter is no longer required.21,22
Recent evidence has demonstrated that catheter size can have an impact on device survival rates. In adults, large-bore catheters of 18 gauge (G) or higher were found to have an increased rate of thrombosis, and smaller-bore catheters of 22G or lower (in adults) were found to have higher rates of dislodgment and occlusion/infiltration. The catheter size recommended for adults based on the latest evidence for most clinical applications is 20G.3,20,23,24 In addition, the documentation of insertion, maintenance, and removal of PIVCs in the medical record is a requirement in most healthcare facilities worldwide and is recommended by best practice guidelines; however, adherence remains a challenge.1,19
The concerning prevalence of PIVC-related complications and the lack of comparative data internationally on organizational compliance with best practice guidelines formed the rationale for this study. Our study aim was to describe the insertion characteristics, management practices, and outcomes of PIVCs internationally and to compare these variables to recommended best practice.
MATERIALS AND METHODS
Study Design and Participants
In this international cross-sectional study, we recruited hospitals through professional networks, including vascular access, infection prevention, safety and quality, nursing, and hospital associations (Appendix 2). Healthcare organizations, government health departments, and intravascular device suppliers were informed of the study and requested to further disseminate information through their networks. A study website was developed,25 and social media outlets, including Twitter®, LinkedIn®, and Facebook®, were used to promote the study.
Approval was granted by the Griffith University Human Research Ethics Committee in Australia (reference number NRS/34/13/HREC). In addition, evidence of study site and local institutional review board/ethics committee approval was required prior to study commencement. Each participating site agreed to follow the study protocol and signed an authorship agreement form. No financial support was provided to any site.
Hospitalized adult and pediatric patients with a PIVC in situ on the day of the study were eligible for inclusion. Sample size was determined by local capacity. Hospitals were encouraged to audit their entire institution if possible; however, data were accepted from as little as one ward. Data collectors comprised nurses and doctors with experience in PIVC assessment. They were briefed on the study protocol and data collection forms by the local site coordinator, and they were supported by an overall global coordinator. Clinicians assessed the PIVC insertion site and accessed hospital records to collect data related to PIVC insertion, concurrent medications, and IV fluid orders. Further clarification of data was obtained if necessary by the clinicians from the patients and treating staff. No identifiable patient information was collected.
Data Collection
To assess whether clinical facilities were following best practice recommendations, the study team developed three data collection forms to collect information regarding site characteristics (site questionnaire), track participant recruitment (screening log), and collect data regarding PIVC characteristics and management practices (case report form [CRF]). All forms were internally and externally validated following a pilot study involving 14 sites in 13 countries.1
The CRF included variables used to assess best practice interventions, such as catheter insertion characteristics (date and time, reason, location, profession of inserter, anatomical site of placement), catheter type (gauge, brand, and product), insertion site assessment (adverse symptoms, dressing type and integrity), and information related to the IV therapy (types of IV fluids and medications, flushing solutions). Idle PIVCs were defined as not being used for blood sampling or IV therapy in the preceding 24 h.
Data collection forms were translated into 15 languages by professional translators and back-translated for validity. Translation of some languages included additional rigor. For example, Spanish-speaking members from the Spanish mainland as well as from South America were employed so that appropriate synonyms were used to capture local terms and practice. Three options were provided for data entry: directly into a purpose-developed electronic database (Lime Survey® Project, Hamburg, Germany); on paper, then transcribed into the survey database at a later time by the hospital site; or paper entry then sent (via email or post) to the coordinating center for data entry. Once cleaned and collated, all data were provided to each participating hospital to confirm accuracy and for site use in local quality improvement processes. Data were collected between June 1, 2014 and July 31, 2015.
Statistical Analysis
All data management was undertaken using SAS statistical software (SAS Institute Inc., Cary NC, USA). Results are presented for eight geographical regions using descriptive statistics (frequencies, percentages, and 95% CIs) for the variables of interest. To assess trends in catheter dwell time and rates of phlebitis, Poisson regression was used. All analyses were undertaken using the R language for statistical analysis (R Core Team, Vienna, Austria). The (STROBE (Strengthening the Reporting of Observational Studies in Epidemiology statement) guidelines for cross-sectional studies were followed, and results are presented according to these recommendations.26
RESULTS
Of the 415 hospitals that participated in this study, 406 had patients with PIVCs on the day of the study (the others being small rural centers). Thus, a total of 40,620 PIVCs in 38,161 patients from 406 hospitals in 51 countries were assessed, with no more than 5% missing data for any CRF question. There were 2459 patients (6.1%) with two or more PIVCs concurrently in situ. The median patient age was 59 y (interquartile range [IQR], 37–74 y), and just over half were male (n = 20,550, 51%). Hospital size ranged from fewer than 10 beds to over 1,000 beds, and hospitals were located in rural, regional, and metropolitan districts. The majority of countries (n = 31, 61%) contributed multiple sites, the highest being Australia with 79 hospitals. Countries with the most PIVCs studied were Spain (n = 5,553, 14%) and the United States (n = 5,048, 12%).
General surgical (n = 15,616, 39%) and medical (n = 15,448, 38%) patients represented most of the population observed. PIVCs were inserted primarily in general wards or clinics (n = 22,167, 55%) or in emergency departments (n = 7,388, 18%; Table) and for the administration of IV medication (n = 28,571, 70%) and IV fluids (n = 7,093, 18%; Table).
Globally, nurses were the primary PIVC inserters (n = 28,575, 71%); however, Australia/New Zealand had only 26% (n = 1,518) of PIVCs inserted by this group (Table). Only about one-third of PIVCs were placed in an area of non-flexion (forearm, n = 12,675, 31%, Table) the majority (n = 27,856, 69%) were placed in non-recommended anatomical sites (Figure 1). Most PIVCs were placed in the hand (n = 13,265, 32.7%) followed by the antecubital veins (n = 6176, 15.2%) and the wrist (n = 5,465, 13.5%). Site selection varied widely across the regions; 29% (n = 1686) of PIVCs in Australia/New Zealand were inserted into the antecubital veins, twice the study group average. Over half of the PIVCs inserted in the Middle East were placed in the hand (n = 295, 56%). This region also had the highest prevalence of devices placed in nonrecommended sites (n = 416, 79%; Figure 1).
The majority of PIVCs (n = 27,192, 67%; Table) were of recommended size (20–22G); however, some devices were observed to be large (14–18G; n = 6,802, 17%) or small (24-26g; n = 4,869, 12%) in adults. In Asia, 41% (n = 2,617) of devices inserted were 24-26G, more than three times the global rate. Half of all devices in Asia (n = 3,077, 48%) and the South Pacific (n = 67, 52%) were of a size not recommended for routine IV therapy (Figure 2).
The primary dressing material used was a transparent dressing (n = 31,596, 77.8%; Table); however, nearly 1 in 5 dressings used had either nonsterile tape alone (n = 5,169, 13%; Appendix 4), or a sterile gauze and tape (n = 2,592, 6%; Appendix 4.1). We found a wide variation in the use of nonsterile tape, including 1 in every 3 devices in South America dressed with nonsterile tape (n = 714, 30%) and a larger proportion in Africa (n = 543, 19%) and Europe (n = 3,056, 18%). Nonsterile tape was rarely used in North America and Australia/New Zealand. Although most PIVC dressings were clean, dry, and intact (n = 31,786, 79%; Table), one-fifth overall were compromised (moist, soiled, and/or lifting off the skin). Compromised dressings (Appendix 4.2) were more prevalent in Australia/New Zealand (n = 1,448; 25%) and in Africa (n = 707, 25%) than elsewhere.
Ten percent of PIVCs (n = 4,204) had signs and/or symptoms suggestive of phlebitis (characterized by pain, redness and/or swelling at the insertion site; Appendix 4.3). The highest prevalence of phlebitis occurred in Asia (n = 1,021, 16%), Africa (n = 360, 13%), and South America (n = 284, 12%). Pain and/or redness were the most common phlebitis symptoms. We found no association between dwell time of PIVCs and phlebitis rates (P = .085). Phlebitis rates were 12% (Days 1-3; n = 15,625), 16% (Days 4-7; n = 3,348), 10% (Days 8-21; n = 457), and 13% (Day21+; n = 174). Nearly 10% (n = 3,879) of catheters were observed to have signs of malfunction such as blood in the infusion tubing, leaking at the insertion site, or dislodgment (Appendix 4.4).
We observed 14% (n = 5,796) of PIVCs to be idle (Appendix 4.5), defined as not used in the preceding 24 h. Nearly one-fourth of all devices in North America (n = 1,230, 23%) and Australia/New Zealand (n = 1,335, 23%) were idle. PIVC documentation in hospital records was also poor, nearly half of all PIVCs (n = 19,768, 49%) had no documented date and time of insertion. The poorest compliance was in Australia/New Zealand (n = 3,428, 59%; Appendix 4.6). We also observed that 1 in 10 PIVCs had no documentation regarding who inserted the PIVC (n = 3,905). Thirty-six percent of PIVCs (n = 14,787) had no documented assessment of the PIVC site on the day of review (Appendix 4.7), including over half of all PIVCs in Asia (n = 3,364, 52%). Overall, the median dwell at the time of assessment for PIVCs with insertion date/time documented was 1.5 d (IQR, 1.0–2.5 d).
DISCUSSION
This international assessment of more than 40,000 PIVCs in 51 countries provides great insight into device characteristics and variation in management practices. Predominantly, PIVCs were inserted by nurses in the general ward environment for IV medication. One in ten PIVCs had at least one symptom of phlebitis, one in ten were dysfunctional, one in five PIVC dressings were compromised, and one in six PIVCs had not been used in the preceding 24 h. Nearly half of the PIVCs audited had the insertion date and time missing.
Regional variation was found in the professions inserting PIVCs, as well as in anatomical placement. In Australia/New Zealand, the proportion of nurses inserting PIVCs was much lower than the study group average (26% vs 71%). Because these countries contributed a substantial number of hospitals to the study, this seems a representative finding and suggests a need for education targeted at nurses for PIVC insertion in this region. The veins in the forearm are recommended as optimal for PIVC insertion in adults, rather than areas of high flexion, because the forearm provides a wide surface area to secure and dress PIVCs. Forearm placement can reduce pain during catheter dwell as well as decrease the risk of accidental removal or occlusion.3,19,27 We found only one-third of PIVCs were placed in the forearm, with most placed in the hand, antecubital veins, or wrist. This highlights an inconsistency with published recommendations and suggests that additional training and technology are required so that staff can better identify and insert PIVCs in the forearm for other than very short-term (procedural) PIVCp;s.19
Phlebitis triggering PIVC failure remains a global clinical challenge with numerous phlebitis definitions and varied assessment techniques.10 The prevalence of phlebitis has been difficult to approximate with varying estimates and definitions in the literature; however, it remains a key predictor of PIVC failure.6,10 Identification of this complication and prompt removal of the device is critical for patient comfort and reducing CABSI risk.5,28 The overall prevalence of phlebitis signs or symptoms (defined in this study as having one or more signs of redness, swelling, or pain surrounding the insertion site) was just over 10%, with pain and/or redness being most prevalent. These compromised PIVCs had not been removed as is recommended for such complications.19,28 Considering that our study was a snapshot at only one time point, the per-catheter incidence of phlebitis would be even higher; interestingly, among PIVCs with a documented insertion date and time, we observed that dwell time did not influence phlebitis rates.
Another concern is that nearly 10% (n = 3,879) of PIVCs were malfunctioning (eg, leaking) but were still in place. To bring these problems into context, around 2 billion PIVCs are used annually worldwide; as a consequence, millions of patients suffer from painful or malfunctioning PIVCs staff had not responded.1,29 The placement of large-bore catheters, and smaller-gauge ones in adults, is known to increase the incidence of malfunction that leads to failure. There are a number of sound clinical reasons for the use of large-bore (eg, resuscitation and rapid fluid replacement) or small-bore (eg, difficult venous access with small superficial veins only visible and palpable) catheters. However, it would be expected that only a small proportion of patients would require these devices, and not one in three devices as we identified. This finding suggests that some PIVCs were inappropriate in size for general IV therapy and may reflect antiquated hospital policies for some clinical cohorts.30,31
Overall, transparent dressings were used to cover the PIVC, but a number of patients were observed to have a sterile gauze and tape dressing (n = 2,592, 6%). Although the latter is less common, both dressing approaches are recommended in clinical practice guidelines because there is a lack of high-quality evidence regarding which is superior.21,22,32 Of concern was the use of nonsterile tape to dress the PIVC (n = 5,169, 12.7%). We found the prevalence of nonsterile tape use to be higher in lower-resourced countries in South America (n = 714, 30%), Africa (n = 543, 19%) and Europe (n = 3,056, 18%) and this was likely related to institutional cost reduction practices.
This finding illustrates an important issue regarding proper PIVC care and management practices in developing nations. It is widely known that access to safe health care in lower-resourced nations is challenging and that rates of mortality related to healthcare-associated infections are much higher. Thus, the differences we found in PIVC management practices in these countries are not surprising.33,34 International health networks such as the Infection Control Africa Network, the International Federation of Infection Control, and the Centers for Disease Control and Prevention can have great influence on ministries of health and clinicians in these countries to develop coordinated efforts for safe and sustainable IV practices to reduce the burden of hospital-acquired infections and related morbidity and mortality.
We found that 14% of all PIVCs had no documented IV medication or IV fluid administered in the previous 24 h, strongly indicating that they were no longer needed. Australia/New Zealand, Europe, and North America were observed to have a higher prevalence of idle catheters than the remaining regions. This suggests that an opportunity exists to develop surveillance systems that better identify idle devices for prompt removal to reduce infection risk and patient discomfort. Several randomized controlled trials, a Cochrane review, and clinical practice guidelines recommend prompt removal of PIVCs when not required, if there are any complications, or if the PIVC was inserted urgently without an aseptic insertion technique.21,28,35,36 Idle PIVCs have been implicated in adverse patient outcomes, including phlebitis and CABSI.13,27
The substantial proportion of patients with a PIVC in this study who had no clinical indication for a PIVC, a symptomatic insertion site, malfunctioning catheter, and suboptimal dressing quality suggests the need for physicians, advanced practitioners, and nurses to adopt evidence-based PIVC insertion and maintenance bundles and supporting checklists to reduce the prevalence of PIVC complications.19,21,38-40 Recommended strategies for inclusion in PIVC maintenance bundles are prompt removal of symptomatic and/or idle catheters, hand hygiene prior to accessing the catheter, regular assessment of the device, and replacement of suboptimal dressings.41,42 This approach should be implemented across all clinical specialties involved in PIVC insertion and care.
Our study findings need to be considered within the context of some limitations. The cross-sectional design prevented follow-up of PIVCs until removal to collect outcomes, including subsequent PIVC complications and/or failure, following the study observation. Ideally, data collection could have included patient-level preferences for PIVC insertion, history of PIVC use and/or failure, the number of PIVC insertion attempts, and the number of PIVCs used during that hospitalization. However, a cohort study of this magnitude was not feasible, particularly because all sites contributed staff time to complete the data collection. Only half of all initially registered sites eventually participated in the study; reasons for not participating were cited as local workload constraints and/or difficulties in applying for local approvals. Although efforts to enroll hospitals worldwide were exhaustive, our sample was not randomly selected but relied on self-selection and so is not representative, particularly for countries that contributed only one hospital site. Caution is also required when comparing inter regional differences, particularly developing regions, because better-resourced/academic sites were possibly over represented in the sample. Nevertheless, PIVC variables differed significantly between participating hospitals, suggesting that the data represent a reasonable reflection of hospital variability.
CONCLUSIONS
On the basis of this international investigation, we report variations in the characteristics, management practices, and outcomes of PIVCs inserted in hospital patients from 51 countries. Many PIVCs were idle, symptomatic, had substandard dressings, and were inserted in suboptimal anatomical sites. Despite international best practice guidelines, a large number of patients had PIVCs that were already failing or at risk of complications, including infection. A stronger focus is needed on compliance with PIVC insertion and management guidelines; better surveillance of PIVC sites; and improved assessment, decision-making, and documentation.
Acknowledgements
We are extremely grateful to colleagues from across the globe who committed their time and effort to this study (for full details of countries and team members see Appendix 1).
1. Alexandrou E, Ray-Barruel G, Carr PJ, et al. International prevalence of the use of peripheral intravenous catheters. J Hosp Med. 2015;10(8):530-533. https:/doi.org/10.1002/jhm.2389
2. Zingg W, Pittet D. Peripheral venous catheters: an under-evaluated problem. Int J Antimicrob Agents. 2009;34(suppl 4):S38-S42. https:/ doi.org/10.1016/S0924-8579(09)70565-5
3. Wallis MC, McGrail MR, Webster J, Gowardman JR, Playford G, Rickard CM. Risk factors for PIV catheter failure: a multivariate analysis from a randomized control trial. Infect. Control Hosp Epidemiol. 2014;35(1):63-68. https:/doi.org/10.1086/674398.
4. Pujol M, Hornero A, Saballs M, et al. Clinical epidemiology and outcomes of peripheral venous catheter-related bloodstream infections at a university-affiliated hospital. J Hosp Infect. 2007;67(1):22-29.
5. Fakih MG, Jones K, Rey JE, et al. Sustained improvements in peripheral venous catheter care in non–intensive care units: a quasi-experimental controlled study of education and feedback. Infect. Control Hosp Epidemiol. 2012;33(5):449-455. https:/doi.org/10.1086/665322.
6. Helm RE, Klausner JD, Klemperer JD, Flint LM, Huang E. Accepted but unacceptable: peripheral IV catheter failure. J Infus Nurs. 2015;38(3):189-203. https:/ doi.org/10.1097/NAN.0000000000000100.
7. Austin ED, Sullivan SB, Whittier S, Lowy FD, Uhlemann AC. Peripheral intravenous catheter placement is an underrecognized source of Staphylococcus aureus bloodstream infection. Open Forum Infect Dis. 2016;3(2):ofw072. https:/ doi.org/10.1093/ofid/ofw072.
8. Stuart RL, Cameron D, Scott C, et al. Peripheral intravenous catheter-associated Staphylococcus aureus bacteraemia: more than 5 years of prospective data from two tertiary health services. Med J Aust. 2013;198(10):551-553.
9. Trinh TT, Chan PA, Edwards O, et al. Peripheral venous catheter-related Staphylococcus aureus bacteremia. Infect Control Hosp Epidemiol. 2011;32(6):579-583. https:/doi.org/10.1086/660099.
10. Ray Barruel G, Polit DF, Murfield JE, Rickard CM. Infusion phlebitis assessment measures: a systematic review. J Eval Clin Pract. 2014;20(2):191-202. https:/ doi.org/ 10.1111/jep.12107
11. Marsh N, Webster J, Flynn J, et al. Securement methods for peripheral venous catheters to prevent failure: a randomised controlled pilot trial. J Vasc Access. 2015;16(3):237-244. https:/doi.org /10.5301/jva.5000348.
12. Carr PJ, Higgins NS, Cooke ML, Rippey J, Rickard CM. Tools, clinical prediction rules, and algorithms for the insertion of peripheral intravenous catheters in adult hospitalized patients: a systematic scoping review of literature. J Hosp Med. 2017;12(10):851-858. https:/doi.org/ 10.12788/jhm.2836
13. Becerra MB, Shirley D, Safdar N. Prevalence, risk factors, and outcomes of idle intravenous catheters: An integrative review. Am J Infect Control. 2016;44(10):e167-e172. https:/ doi.org/10.1016/j.ajic.2016.03.073.
14. Robinson-Reilly M, Paliadelis P, Cruickshank M. Venous access: the patient experience. Support Care Cancer. 2016;24(3):1181-1187. https:/ doi.org/10.1007/s00520-015-2900-9.
15. Petroski A, Frisch A, Joseph N, Carlson JN. Predictors of difficult pediatric intravenous access in a community Emergency Department. J Vasc Access. 2015;16(6):521-526. https:/doi.org/10.5301/jva.5000411
16. Sou V, McManus C, Mifflin N, Frost SA, Ale J, Alexandrou E. A clinical pathway for the management of difficult venous access. BMC Nurs. 2017;16(1):64. https:/ doi.org/10.1186/s12912-017-0261-z
17. World Health Organization. Report on the burden of endemic health care-associated infection worldwide. Geneva2011. 9241501502.
18. Hirschmann H, Fux L, Podusel J, et al. The influence of hand hygiene prior to insertion of peripheral venous catheters on the frequency of complications. J Hosp Infect. 2001;49(3):199-203. https:/doi.org/10.1053/jhin.2001.1077
19. Gorski L, Hadaway L, Hagle M, McGoldrick M, Orr M, Doellman D. Infusion therapy standards of practice. J Infus Nurs. 2016;39(suppl 1):S1-S159.
20. Abolfotouh MA, Salam M, Bani-Mustafa Aa, White D, Balkhy HH. Prospective study of incidence and predictors of peripheral intravenous catheter-induced complications. Ther Clin Risk Manag. 2014;10:993. https://doi.org/10.2147/TCRM.S74685.
21. Loveday H, Wilson J, Pratt R, et al. epic3: national evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England. J Hosp Infect. 2014;86(suppl 1):S1-S70. https:/doi.org/10.1016/S0195-6701(13)60012-2.
22. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis. 2011;52(9):e162-e193. https:/doi.org/10.1093/cid/cir257
23. Cicolini G, Bonghi AP, Di Labio L, Di Mascio R. Position of peripheral venous cannulae and the incidence of thrombophlebitis: an observational study. J Adv Nurs. 2009;65(6):1268-1273. https:/doi.org/10.1111/j.1365-2648.2009.04980.x.
24. Marsh N, Webster J, Larson E, Cooke M, Mihala G, Rickard C. Observational study of peripheral intravenous catheter outcomes in adult hospitalized patients: a multivariable analysis of peripheral intravenous catheter failure. J Hosp Med. 2018;13(2):83-89. https:/doi.org/10.12788/jhm.2867.
25. One Million Global Catheters PIVC Worldwide Prevalence study. OMG study website http://www.omgpivc.org/. Accessed 23 March, 2017.
26. Von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg. 2014;12(12):1495-1499. https:/doi.org/ 10.1136/bmj.39335.541782.AD
27. Fields JM, Dean AJ, Todman RW, et al. The effect of vessel depth, diameter, and location on ultrasound-guided peripheral intravenous catheter longevity. Am J Emerg Med. 2012;30(7):1134-1140. https:/doi.org/10.1016/j.ajem.2011.07.027.
28. Patel SA, Alebich MM, Feldman LS. Choosing wisely: things we do for no reason. Routine replacement of peripheral intravenous catheters. J Hosp Med. 2017;12(1):42-45.
29. Newswire. Global Peripheral I.V. Catheter Market 2014 - 2018. New York, PR Newswire Assoc; 2014.
30. Webster J, Larsen E, Booker C, Laws J, Marsh N. Prophylactic insertion of large bore peripheral intravenous catheters in maternity patients for postpartum haemorrhage: A cohort study. Aust N Z J Obstet Gynaecol. 2017.https:/doi.org/10.1111/ajo.12759.
31. Rivera A, Strauss K, van Zundert A, Mortier E. Matching the peripheral intravenous catheter to the individual patient. Acta Anaesthesiol Belg. 2006;58(1):19.
32. Webster J, Gillies D, O’Riordan E, Sherriff KL, Rickard CM. Gauze and tape and transparent polyurethane dressings for central venous catheters. Cochrane Database Syst Rev. 2011;11:CD003827. https:/doi.org/10.1002/14651858.CD003827.pub2
33. Dieleman JL, Templin T, Sadat N, et al. National spending on health by source for 184 countries between 2013 and 2040. Lancet. 2016;387(10037):2521-2535. https:/ doi.org/10.1016/S0140-6736(16)30167-2.
34. Allegranzi B, Nejad SB, Combescure C, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet. 2011;377(9761):228-241. https:/ doi.org/10.1016/S0140-6736(10)61458-4.
35. Rickard CM, Webster J, Wallis MC, et al. Routine versus clinically indicated replacement of peripheral intravenous catheters: a randomised controlled equivalence trial. Lancet. 2012;380(9847):1066-1074. https:/doi.org/10.1016/S0140-6736(12)61082-4.
36. Webster J, Osborne S, Rickard CM, New K. Clinically indicated replacement versus routine replacement of peripheral venous catheters. Cochrane Database Syst Rev. 2015;8:CD007798. https://doi.org/10.1002/14651858.CD007798.pub4.
37. Yagnik L, Graves A, Thong K. Plastic in patient study: Prospective audit of adherence to peripheral intravenous cannula monitoring and documentation guidelines, with the aim of reducing future rates of intravenous cannula-related complications. Am J Infect Control. 2017;45(1):34-38. https:/doi.org/10.1016/j.ajic.2016.09.008.
38. Boyd S, Aggarwal I, Davey P, Logan M, Nathwani D. Peripheral intravenous catheters: the road to quality improvement and safer patient care. J Hosp Infect. 2011;77(1):37-41. https:/doi.org/10.1016/j.jhin.2010.09.011.
39. DeVries M, Valentine M, Mancos P. Protected clinical indication of peripheral intravenous lines: successful implementation. J Assoc Vasc Access. 2016;21(2):89-92. https://doi.org/10.1016/j.java.2016.03.001.
40. Rhodes D, Cheng A, McLellan S, et al. Reducing Staphylococcus aureus bloodstream infections associated with peripheral intravenous cannulae: successful implementation of a care bundle at a large Australian health service. J Hosp Infect. 2016;94(1):86-91. https:/doi.org/10.1016/j.jhin.2016.05.020.
41. Rinke ML, Chen AR, Bundy DG, et al. Implementation of a central line maintenance care bundle in hospitalized pediatric oncology patients. Pediatr. 2012;130(4):e996-e1004. https:/doi.org/10.1542/peds.2012-0295.
42. Marshall J, Mermel L, Fakih M, Hadaway L, Kallen A, O’Grady N. Strategies to prevent central line–associated bloodstream infections in acute care hospitals: 2014 update. Infect. Control Hosp Epidemiol. 2014;35(suppl 2):S89-107. https:/doi.org/10.1086/676533.
1. Alexandrou E, Ray-Barruel G, Carr PJ, et al. International prevalence of the use of peripheral intravenous catheters. J Hosp Med. 2015;10(8):530-533. https:/doi.org/10.1002/jhm.2389
2. Zingg W, Pittet D. Peripheral venous catheters: an under-evaluated problem. Int J Antimicrob Agents. 2009;34(suppl 4):S38-S42. https:/ doi.org/10.1016/S0924-8579(09)70565-5
3. Wallis MC, McGrail MR, Webster J, Gowardman JR, Playford G, Rickard CM. Risk factors for PIV catheter failure: a multivariate analysis from a randomized control trial. Infect. Control Hosp Epidemiol. 2014;35(1):63-68. https:/doi.org/10.1086/674398.
4. Pujol M, Hornero A, Saballs M, et al. Clinical epidemiology and outcomes of peripheral venous catheter-related bloodstream infections at a university-affiliated hospital. J Hosp Infect. 2007;67(1):22-29.
5. Fakih MG, Jones K, Rey JE, et al. Sustained improvements in peripheral venous catheter care in non–intensive care units: a quasi-experimental controlled study of education and feedback. Infect. Control Hosp Epidemiol. 2012;33(5):449-455. https:/doi.org/10.1086/665322.
6. Helm RE, Klausner JD, Klemperer JD, Flint LM, Huang E. Accepted but unacceptable: peripheral IV catheter failure. J Infus Nurs. 2015;38(3):189-203. https:/ doi.org/10.1097/NAN.0000000000000100.
7. Austin ED, Sullivan SB, Whittier S, Lowy FD, Uhlemann AC. Peripheral intravenous catheter placement is an underrecognized source of Staphylococcus aureus bloodstream infection. Open Forum Infect Dis. 2016;3(2):ofw072. https:/ doi.org/10.1093/ofid/ofw072.
8. Stuart RL, Cameron D, Scott C, et al. Peripheral intravenous catheter-associated Staphylococcus aureus bacteraemia: more than 5 years of prospective data from two tertiary health services. Med J Aust. 2013;198(10):551-553.
9. Trinh TT, Chan PA, Edwards O, et al. Peripheral venous catheter-related Staphylococcus aureus bacteremia. Infect Control Hosp Epidemiol. 2011;32(6):579-583. https:/doi.org/10.1086/660099.
10. Ray Barruel G, Polit DF, Murfield JE, Rickard CM. Infusion phlebitis assessment measures: a systematic review. J Eval Clin Pract. 2014;20(2):191-202. https:/ doi.org/ 10.1111/jep.12107
11. Marsh N, Webster J, Flynn J, et al. Securement methods for peripheral venous catheters to prevent failure: a randomised controlled pilot trial. J Vasc Access. 2015;16(3):237-244. https:/doi.org /10.5301/jva.5000348.
12. Carr PJ, Higgins NS, Cooke ML, Rippey J, Rickard CM. Tools, clinical prediction rules, and algorithms for the insertion of peripheral intravenous catheters in adult hospitalized patients: a systematic scoping review of literature. J Hosp Med. 2017;12(10):851-858. https:/doi.org/ 10.12788/jhm.2836
13. Becerra MB, Shirley D, Safdar N. Prevalence, risk factors, and outcomes of idle intravenous catheters: An integrative review. Am J Infect Control. 2016;44(10):e167-e172. https:/ doi.org/10.1016/j.ajic.2016.03.073.
14. Robinson-Reilly M, Paliadelis P, Cruickshank M. Venous access: the patient experience. Support Care Cancer. 2016;24(3):1181-1187. https:/ doi.org/10.1007/s00520-015-2900-9.
15. Petroski A, Frisch A, Joseph N, Carlson JN. Predictors of difficult pediatric intravenous access in a community Emergency Department. J Vasc Access. 2015;16(6):521-526. https:/doi.org/10.5301/jva.5000411
16. Sou V, McManus C, Mifflin N, Frost SA, Ale J, Alexandrou E. A clinical pathway for the management of difficult venous access. BMC Nurs. 2017;16(1):64. https:/ doi.org/10.1186/s12912-017-0261-z
17. World Health Organization. Report on the burden of endemic health care-associated infection worldwide. Geneva2011. 9241501502.
18. Hirschmann H, Fux L, Podusel J, et al. The influence of hand hygiene prior to insertion of peripheral venous catheters on the frequency of complications. J Hosp Infect. 2001;49(3):199-203. https:/doi.org/10.1053/jhin.2001.1077
19. Gorski L, Hadaway L, Hagle M, McGoldrick M, Orr M, Doellman D. Infusion therapy standards of practice. J Infus Nurs. 2016;39(suppl 1):S1-S159.
20. Abolfotouh MA, Salam M, Bani-Mustafa Aa, White D, Balkhy HH. Prospective study of incidence and predictors of peripheral intravenous catheter-induced complications. Ther Clin Risk Manag. 2014;10:993. https://doi.org/10.2147/TCRM.S74685.
21. Loveday H, Wilson J, Pratt R, et al. epic3: national evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England. J Hosp Infect. 2014;86(suppl 1):S1-S70. https:/doi.org/10.1016/S0195-6701(13)60012-2.
22. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis. 2011;52(9):e162-e193. https:/doi.org/10.1093/cid/cir257
23. Cicolini G, Bonghi AP, Di Labio L, Di Mascio R. Position of peripheral venous cannulae and the incidence of thrombophlebitis: an observational study. J Adv Nurs. 2009;65(6):1268-1273. https:/doi.org/10.1111/j.1365-2648.2009.04980.x.
24. Marsh N, Webster J, Larson E, Cooke M, Mihala G, Rickard C. Observational study of peripheral intravenous catheter outcomes in adult hospitalized patients: a multivariable analysis of peripheral intravenous catheter failure. J Hosp Med. 2018;13(2):83-89. https:/doi.org/10.12788/jhm.2867.
25. One Million Global Catheters PIVC Worldwide Prevalence study. OMG study website http://www.omgpivc.org/. Accessed 23 March, 2017.
26. Von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg. 2014;12(12):1495-1499. https:/doi.org/ 10.1136/bmj.39335.541782.AD
27. Fields JM, Dean AJ, Todman RW, et al. The effect of vessel depth, diameter, and location on ultrasound-guided peripheral intravenous catheter longevity. Am J Emerg Med. 2012;30(7):1134-1140. https:/doi.org/10.1016/j.ajem.2011.07.027.
28. Patel SA, Alebich MM, Feldman LS. Choosing wisely: things we do for no reason. Routine replacement of peripheral intravenous catheters. J Hosp Med. 2017;12(1):42-45.
29. Newswire. Global Peripheral I.V. Catheter Market 2014 - 2018. New York, PR Newswire Assoc; 2014.
30. Webster J, Larsen E, Booker C, Laws J, Marsh N. Prophylactic insertion of large bore peripheral intravenous catheters in maternity patients for postpartum haemorrhage: A cohort study. Aust N Z J Obstet Gynaecol. 2017.https:/doi.org/10.1111/ajo.12759.
31. Rivera A, Strauss K, van Zundert A, Mortier E. Matching the peripheral intravenous catheter to the individual patient. Acta Anaesthesiol Belg. 2006;58(1):19.
32. Webster J, Gillies D, O’Riordan E, Sherriff KL, Rickard CM. Gauze and tape and transparent polyurethane dressings for central venous catheters. Cochrane Database Syst Rev. 2011;11:CD003827. https:/doi.org/10.1002/14651858.CD003827.pub2
33. Dieleman JL, Templin T, Sadat N, et al. National spending on health by source for 184 countries between 2013 and 2040. Lancet. 2016;387(10037):2521-2535. https:/ doi.org/10.1016/S0140-6736(16)30167-2.
34. Allegranzi B, Nejad SB, Combescure C, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet. 2011;377(9761):228-241. https:/ doi.org/10.1016/S0140-6736(10)61458-4.
35. Rickard CM, Webster J, Wallis MC, et al. Routine versus clinically indicated replacement of peripheral intravenous catheters: a randomised controlled equivalence trial. Lancet. 2012;380(9847):1066-1074. https:/doi.org/10.1016/S0140-6736(12)61082-4.
36. Webster J, Osborne S, Rickard CM, New K. Clinically indicated replacement versus routine replacement of peripheral venous catheters. Cochrane Database Syst Rev. 2015;8:CD007798. https://doi.org/10.1002/14651858.CD007798.pub4.
37. Yagnik L, Graves A, Thong K. Plastic in patient study: Prospective audit of adherence to peripheral intravenous cannula monitoring and documentation guidelines, with the aim of reducing future rates of intravenous cannula-related complications. Am J Infect Control. 2017;45(1):34-38. https:/doi.org/10.1016/j.ajic.2016.09.008.
38. Boyd S, Aggarwal I, Davey P, Logan M, Nathwani D. Peripheral intravenous catheters: the road to quality improvement and safer patient care. J Hosp Infect. 2011;77(1):37-41. https:/doi.org/10.1016/j.jhin.2010.09.011.
39. DeVries M, Valentine M, Mancos P. Protected clinical indication of peripheral intravenous lines: successful implementation. J Assoc Vasc Access. 2016;21(2):89-92. https://doi.org/10.1016/j.java.2016.03.001.
40. Rhodes D, Cheng A, McLellan S, et al. Reducing Staphylococcus aureus bloodstream infections associated with peripheral intravenous cannulae: successful implementation of a care bundle at a large Australian health service. J Hosp Infect. 2016;94(1):86-91. https:/doi.org/10.1016/j.jhin.2016.05.020.
41. Rinke ML, Chen AR, Bundy DG, et al. Implementation of a central line maintenance care bundle in hospitalized pediatric oncology patients. Pediatr. 2012;130(4):e996-e1004. https:/doi.org/10.1542/peds.2012-0295.
42. Marshall J, Mermel L, Fakih M, Hadaway L, Kallen A, O’Grady N. Strategies to prevent central line–associated bloodstream infections in acute care hospitals: 2014 update. Infect. Control Hosp Epidemiol. 2014;35(suppl 2):S89-107. https:/doi.org/10.1086/676533.
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A New Target for a Flu Vaccine?
Seasonal flu vaccines mainly target an influenza surface protein called hemagglutinin (HA). But new research from National Institute of Health (NIH) studies suggest that it might be better to target a surface protein called neuraminidase (NA) for broader protection.
Researchers analyzed blood samples from people vaccinated against influenza and people who were diagnosed with the 2009 H1N1 virus or H3N2 viruses. The analyses indicated that influenza vaccines rarely induce NA-reactive antibodies, whereas natural influenza infection induces these types of antibodies at least as often as it induces HA-reactive antibodies, the researchers say.
Additional laboratory experiments showed the NA-reactive antibodies induced during natural flu infection were “broadly reactive,” meaning they could potentially protect against diverse strains. To test that theory, the researchers isolated NA-reactive monoclonal antibodies from the patients with H3N2 and H1N1, then administered 13 N2-reactive antibodies to mice and infected the mice with a different H3N2 virus strain. Eleven of the N2-reactive antibodies partially or fully protected the mice. In a similar test of N1-reactive antibodies versus H1N1 virus and H5N1-like virus, 4 of 8 antibodies completely protected against both strains.
Seasonal flu vaccines mainly target an influenza surface protein called hemagglutinin (HA). But new research from National Institute of Health (NIH) studies suggest that it might be better to target a surface protein called neuraminidase (NA) for broader protection.
Researchers analyzed blood samples from people vaccinated against influenza and people who were diagnosed with the 2009 H1N1 virus or H3N2 viruses. The analyses indicated that influenza vaccines rarely induce NA-reactive antibodies, whereas natural influenza infection induces these types of antibodies at least as often as it induces HA-reactive antibodies, the researchers say.
Additional laboratory experiments showed the NA-reactive antibodies induced during natural flu infection were “broadly reactive,” meaning they could potentially protect against diverse strains. To test that theory, the researchers isolated NA-reactive monoclonal antibodies from the patients with H3N2 and H1N1, then administered 13 N2-reactive antibodies to mice and infected the mice with a different H3N2 virus strain. Eleven of the N2-reactive antibodies partially or fully protected the mice. In a similar test of N1-reactive antibodies versus H1N1 virus and H5N1-like virus, 4 of 8 antibodies completely protected against both strains.
Seasonal flu vaccines mainly target an influenza surface protein called hemagglutinin (HA). But new research from National Institute of Health (NIH) studies suggest that it might be better to target a surface protein called neuraminidase (NA) for broader protection.
Researchers analyzed blood samples from people vaccinated against influenza and people who were diagnosed with the 2009 H1N1 virus or H3N2 viruses. The analyses indicated that influenza vaccines rarely induce NA-reactive antibodies, whereas natural influenza infection induces these types of antibodies at least as often as it induces HA-reactive antibodies, the researchers say.
Additional laboratory experiments showed the NA-reactive antibodies induced during natural flu infection were “broadly reactive,” meaning they could potentially protect against diverse strains. To test that theory, the researchers isolated NA-reactive monoclonal antibodies from the patients with H3N2 and H1N1, then administered 13 N2-reactive antibodies to mice and infected the mice with a different H3N2 virus strain. Eleven of the N2-reactive antibodies partially or fully protected the mice. In a similar test of N1-reactive antibodies versus H1N1 virus and H5N1-like virus, 4 of 8 antibodies completely protected against both strains.
Study of daratumamb with anti-PD-1 antibody in MM discontinued
Janssen is discontinuing the phase 1 MMY2036 study of daratumumab in combination with the anti PD-1 antibody JNJ-63723283 in patients with multiple myeloma (MM).
Janssen made the decision based on a Data Monitoring Committee review of Genmab’s phase 1b/2 study (LUC2001) of daratumumab plus the anti-PD-L1 antibody atezolizumab in non-small cell lung cancer (NSCLC).
Based on the DMC findings, Janssen also decided to discontinue its daratumumab-PD-1 combination study.
Janssen has an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.
In the planned review, the DMC determined there was no observed benefit within the daratumumab plus atezolizumab arm compared to the atezolizumab monotherapy arm. The DMC recommended termination of the NSCLC study.
The DMC also noted an increase in mortality-related events in the combination arm.
Janssen has informed health authorities about these events and has contacted its partner companies conducting daratumumab and anti-PD-1 combination studies to discuss ceasing enrollment and dosing of the combination while the data is being further investigated.
MMY2036 study (NCT03357952)
The randomized, multicenter, multiphase study was expected to enroll up to 386 patients with relapsed or refractory MM who had received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory (IMiD) agent. Refractory patients had to be double refractory to both a PI and an IMiD.
The trial was to be conducted in 3 parts. Part 1 was to assess the safety of the combination of JNJ-63723283 and daratumumab. Part 2 was intended to compare the overall response rate in patients treated with the combination compared to those treated with daratumumab alone. And Part 3 was to compare progression-free survival between the 2 arms.
Daratumumab dose was planned to be 16 mg/kg weekly for 8 weeks, then once every other week for 16 weeks; then once every 4 weeks.
JNJ-63723283 dose was planned to be 240 milligrams IV fixed dose during week 1 on cycle 1 (28 days) day 2, cycle 1 day 15, then every 2 weeks thereafter.
The study was started in November 2017 and planned to be completed in December 2019.
In a news release, Genmab’s chief executive officer, Jan van de Winkel, PhD, expressed disappointment that the studies will be discontinued. He said Genmab “fully supports Janssen’s decision as patient safety is paramount in drug development. We look forward to gaining a better understanding of the data upon further analysis.”
Janssen is discontinuing the phase 1 MMY2036 study of daratumumab in combination with the anti PD-1 antibody JNJ-63723283 in patients with multiple myeloma (MM).
Janssen made the decision based on a Data Monitoring Committee review of Genmab’s phase 1b/2 study (LUC2001) of daratumumab plus the anti-PD-L1 antibody atezolizumab in non-small cell lung cancer (NSCLC).
Based on the DMC findings, Janssen also decided to discontinue its daratumumab-PD-1 combination study.
Janssen has an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.
In the planned review, the DMC determined there was no observed benefit within the daratumumab plus atezolizumab arm compared to the atezolizumab monotherapy arm. The DMC recommended termination of the NSCLC study.
The DMC also noted an increase in mortality-related events in the combination arm.
Janssen has informed health authorities about these events and has contacted its partner companies conducting daratumumab and anti-PD-1 combination studies to discuss ceasing enrollment and dosing of the combination while the data is being further investigated.
MMY2036 study (NCT03357952)
The randomized, multicenter, multiphase study was expected to enroll up to 386 patients with relapsed or refractory MM who had received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory (IMiD) agent. Refractory patients had to be double refractory to both a PI and an IMiD.
The trial was to be conducted in 3 parts. Part 1 was to assess the safety of the combination of JNJ-63723283 and daratumumab. Part 2 was intended to compare the overall response rate in patients treated with the combination compared to those treated with daratumumab alone. And Part 3 was to compare progression-free survival between the 2 arms.
Daratumumab dose was planned to be 16 mg/kg weekly for 8 weeks, then once every other week for 16 weeks; then once every 4 weeks.
JNJ-63723283 dose was planned to be 240 milligrams IV fixed dose during week 1 on cycle 1 (28 days) day 2, cycle 1 day 15, then every 2 weeks thereafter.
The study was started in November 2017 and planned to be completed in December 2019.
In a news release, Genmab’s chief executive officer, Jan van de Winkel, PhD, expressed disappointment that the studies will be discontinued. He said Genmab “fully supports Janssen’s decision as patient safety is paramount in drug development. We look forward to gaining a better understanding of the data upon further analysis.”
Janssen is discontinuing the phase 1 MMY2036 study of daratumumab in combination with the anti PD-1 antibody JNJ-63723283 in patients with multiple myeloma (MM).
Janssen made the decision based on a Data Monitoring Committee review of Genmab’s phase 1b/2 study (LUC2001) of daratumumab plus the anti-PD-L1 antibody atezolizumab in non-small cell lung cancer (NSCLC).
Based on the DMC findings, Janssen also decided to discontinue its daratumumab-PD-1 combination study.
Janssen has an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.
In the planned review, the DMC determined there was no observed benefit within the daratumumab plus atezolizumab arm compared to the atezolizumab monotherapy arm. The DMC recommended termination of the NSCLC study.
The DMC also noted an increase in mortality-related events in the combination arm.
Janssen has informed health authorities about these events and has contacted its partner companies conducting daratumumab and anti-PD-1 combination studies to discuss ceasing enrollment and dosing of the combination while the data is being further investigated.
MMY2036 study (NCT03357952)
The randomized, multicenter, multiphase study was expected to enroll up to 386 patients with relapsed or refractory MM who had received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory (IMiD) agent. Refractory patients had to be double refractory to both a PI and an IMiD.
The trial was to be conducted in 3 parts. Part 1 was to assess the safety of the combination of JNJ-63723283 and daratumumab. Part 2 was intended to compare the overall response rate in patients treated with the combination compared to those treated with daratumumab alone. And Part 3 was to compare progression-free survival between the 2 arms.
Daratumumab dose was planned to be 16 mg/kg weekly for 8 weeks, then once every other week for 16 weeks; then once every 4 weeks.
JNJ-63723283 dose was planned to be 240 milligrams IV fixed dose during week 1 on cycle 1 (28 days) day 2, cycle 1 day 15, then every 2 weeks thereafter.
The study was started in November 2017 and planned to be completed in December 2019.
In a news release, Genmab’s chief executive officer, Jan van de Winkel, PhD, expressed disappointment that the studies will be discontinued. He said Genmab “fully supports Janssen’s decision as patient safety is paramount in drug development. We look forward to gaining a better understanding of the data upon further analysis.”