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Therapy receives orphan designation for hemophilia A
The US Food and Drug Administration (FDA) has granted orphan drug designation for SB-525 as a treatment for hemophilia A.
SB-525 is a recombinant adeno-associated virus 2/6 (AAV2/6) vector that expresses a human F8 complementary DNA (cDNA) cassette.
The vector encodes a liver-specific promoter module, and AAV2/6 exhibits liver tropism.
This provides the potential for long-term hepatic production of factor VIII in patients with hemophilia A, according to Sangamo Therapeutics, Inc., the company developing SB-525.
In research presented at the 2016 ASH Annual Meeting (abstract 1173), SB-525 induced the expression of significant levels of human factor VIII in mice and non-human primates (NHPs). SB-525 also corrected the bleeding defect in a mouse model of hemophilia A.
Dosing studies in NHPs demonstrated a robust and reproducible dose response curve, according to researchers. In these animals, mean human factor VIII levels ranged from 5% of normal at the lowest dose to 230% at the highest (AAV doses in the 6 x 1011 – 6 x 1012 vgs/kg range).
The researchers said the peak circulating human factor VIII levels in these experiments exceeded levels previously reported in NHPs. And this could significantly reduce the dose required to achieve therapeutically relevant levels in human subjects.
Sangamo is planning to open a phase 1/2 trial of SB-525 in adults with hemophilia A later this quarter.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 
The US Food and Drug Administration (FDA) has granted orphan drug designation for SB-525 as a treatment for hemophilia A.
SB-525 is a recombinant adeno-associated virus 2/6 (AAV2/6) vector that expresses a human F8 complementary DNA (cDNA) cassette.
The vector encodes a liver-specific promoter module, and AAV2/6 exhibits liver tropism.
This provides the potential for long-term hepatic production of factor VIII in patients with hemophilia A, according to Sangamo Therapeutics, Inc., the company developing SB-525.
In research presented at the 2016 ASH Annual Meeting (abstract 1173), SB-525 induced the expression of significant levels of human factor VIII in mice and non-human primates (NHPs). SB-525 also corrected the bleeding defect in a mouse model of hemophilia A.
Dosing studies in NHPs demonstrated a robust and reproducible dose response curve, according to researchers. In these animals, mean human factor VIII levels ranged from 5% of normal at the lowest dose to 230% at the highest (AAV doses in the 6 x 1011 – 6 x 1012 vgs/kg range).
The researchers said the peak circulating human factor VIII levels in these experiments exceeded levels previously reported in NHPs. And this could significantly reduce the dose required to achieve therapeutically relevant levels in human subjects.
Sangamo is planning to open a phase 1/2 trial of SB-525 in adults with hemophilia A later this quarter.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation for SB-525 as a treatment for hemophilia A.
SB-525 is a recombinant adeno-associated virus 2/6 (AAV2/6) vector that expresses a human F8 complementary DNA (cDNA) cassette.
The vector encodes a liver-specific promoter module, and AAV2/6 exhibits liver tropism.
This provides the potential for long-term hepatic production of factor VIII in patients with hemophilia A, according to Sangamo Therapeutics, Inc., the company developing SB-525.
In research presented at the 2016 ASH Annual Meeting (abstract 1173), SB-525 induced the expression of significant levels of human factor VIII in mice and non-human primates (NHPs). SB-525 also corrected the bleeding defect in a mouse model of hemophilia A.
Dosing studies in NHPs demonstrated a robust and reproducible dose response curve, according to researchers. In these animals, mean human factor VIII levels ranged from 5% of normal at the lowest dose to 230% at the highest (AAV doses in the 6 x 1011 – 6 x 1012 vgs/kg range).
The researchers said the peak circulating human factor VIII levels in these experiments exceeded levels previously reported in NHPs. And this could significantly reduce the dose required to achieve therapeutically relevant levels in human subjects.
Sangamo is planning to open a phase 1/2 trial of SB-525 in adults with hemophilia A later this quarter.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
FDA grants therapy fast track status for hemophilia B
The US Food and Drug Administration (FDA) has granted fast track designation to SB-FIX for the treatment of hemophilia B.
SB-FIX is a zinc finger nuclease (ZFN)-mediated genome-editing product candidate.
It is designed to be used as a one-time treatment that will provide stable, continuous production of factor IX (FIX) for the lifetime of the patient.
The ZFN-mediated in vivo genome-editing approach makes use of the albumin gene locus, a highly expressing and liver-specific genomic “safe-harbor site,” that can be edited with ZFNs to accept and express therapeutic genes.
The approach is designed to enable the patient’s liver to permanently produce circulating therapeutic levels of a corrective protein product.
This differs from conventional adeno-associated virus complementary DNA gene therapy approaches, which are non-integrating and may “wash out” of the liver as cells divide and turn over.
Sangamo Therapeutics, Inc., the company developing SB-FIX, has initiated a phase 1/2 trial of SB-FIX in adults with hemophilia B. The trial is open, and subjects are being screened for enrollment.
In addition to fast track designation, SB-FIX has orphan designation from the FDA (granted in 2016).
About fast track designation
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologic license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted fast track designation to SB-FIX for the treatment of hemophilia B.
SB-FIX is a zinc finger nuclease (ZFN)-mediated genome-editing product candidate.
It is designed to be used as a one-time treatment that will provide stable, continuous production of factor IX (FIX) for the lifetime of the patient.
The ZFN-mediated in vivo genome-editing approach makes use of the albumin gene locus, a highly expressing and liver-specific genomic “safe-harbor site,” that can be edited with ZFNs to accept and express therapeutic genes.
The approach is designed to enable the patient’s liver to permanently produce circulating therapeutic levels of a corrective protein product.
This differs from conventional adeno-associated virus complementary DNA gene therapy approaches, which are non-integrating and may “wash out” of the liver as cells divide and turn over.
Sangamo Therapeutics, Inc., the company developing SB-FIX, has initiated a phase 1/2 trial of SB-FIX in adults with hemophilia B. The trial is open, and subjects are being screened for enrollment.
In addition to fast track designation, SB-FIX has orphan designation from the FDA (granted in 2016).
About fast track designation
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologic license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted fast track designation to SB-FIX for the treatment of hemophilia B.
SB-FIX is a zinc finger nuclease (ZFN)-mediated genome-editing product candidate.
It is designed to be used as a one-time treatment that will provide stable, continuous production of factor IX (FIX) for the lifetime of the patient.
The ZFN-mediated in vivo genome-editing approach makes use of the albumin gene locus, a highly expressing and liver-specific genomic “safe-harbor site,” that can be edited with ZFNs to accept and express therapeutic genes.
The approach is designed to enable the patient’s liver to permanently produce circulating therapeutic levels of a corrective protein product.
This differs from conventional adeno-associated virus complementary DNA gene therapy approaches, which are non-integrating and may “wash out” of the liver as cells divide and turn over.
Sangamo Therapeutics, Inc., the company developing SB-FIX, has initiated a phase 1/2 trial of SB-FIX in adults with hemophilia B. The trial is open, and subjects are being screened for enrollment.
In addition to fast track designation, SB-FIX has orphan designation from the FDA (granted in 2016).
About fast track designation
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologic license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
Tablet-based medical training program improves exam results
Tablet-based, multimedia-enhanced medical training improves examination results among medical students and residents, according to research published in PLOS ONE.
“Ideally, medical training should be taking place at the patient’s bedside rather than in lecture halls,” said study author Daniel C. Baumgart, MD, PhD, of Charité Medical School at Humboldt-University of Berlin in Germany.
“Communication devices, such as tablet computers, digital assistants, and smartphones, make medical data and learning materials available anywhere and anytime. Therefore, our aim was to study the impact of a systematic integration of such devices into medical teaching and training.”
The researchers studied 55 final-year medical students and medical residents doing an inpatient service rotation. The subjects were assigned to receive a tablet personal computer (PC) with a custom multimedia education software package (n=24) or to a control group (n=31).
The multimedia package tested included the Mobile Medical Educator software package (developed in-house) as well as other multimedia learning materials, such as eBooks, eJournals, slide kits, podcasts, videos, animations, image data, and the American College of Physicians’ validated self-assessment software.
The participants had to complete MKSAP® (medical knowledge self-assessment program) exams at the beginning and the end of their training rotations. The final MKSAP score was the study’s primary endpoint.
The mean MKSAP score improved in the tablet PC group but not the control group. The final mean score was significantly higher in the tablet PC group than the control group—59 and 48, respectively (P<0.001).
When the researchers adjusted their analysis for subjects’ baseline score and potential confounders, the tablet PC group had, on average, 11% better MKSAP test results than the control group (P<0.001).
“We were able to show improvements in internal medicine exam results, which were independent of socio-demographic factors,” Dr Baumgart said. “Participant feedback was particularly positive in relation to an integrated, fully digitized workflow for clinical practice and training.”
Tablet-based, multimedia-enhanced medical training improves examination results among medical students and residents, according to research published in PLOS ONE.
“Ideally, medical training should be taking place at the patient’s bedside rather than in lecture halls,” said study author Daniel C. Baumgart, MD, PhD, of Charité Medical School at Humboldt-University of Berlin in Germany.
“Communication devices, such as tablet computers, digital assistants, and smartphones, make medical data and learning materials available anywhere and anytime. Therefore, our aim was to study the impact of a systematic integration of such devices into medical teaching and training.”
The researchers studied 55 final-year medical students and medical residents doing an inpatient service rotation. The subjects were assigned to receive a tablet personal computer (PC) with a custom multimedia education software package (n=24) or to a control group (n=31).
The multimedia package tested included the Mobile Medical Educator software package (developed in-house) as well as other multimedia learning materials, such as eBooks, eJournals, slide kits, podcasts, videos, animations, image data, and the American College of Physicians’ validated self-assessment software.
The participants had to complete MKSAP® (medical knowledge self-assessment program) exams at the beginning and the end of their training rotations. The final MKSAP score was the study’s primary endpoint.
The mean MKSAP score improved in the tablet PC group but not the control group. The final mean score was significantly higher in the tablet PC group than the control group—59 and 48, respectively (P<0.001).
When the researchers adjusted their analysis for subjects’ baseline score and potential confounders, the tablet PC group had, on average, 11% better MKSAP test results than the control group (P<0.001).
“We were able to show improvements in internal medicine exam results, which were independent of socio-demographic factors,” Dr Baumgart said. “Participant feedback was particularly positive in relation to an integrated, fully digitized workflow for clinical practice and training.”
Tablet-based, multimedia-enhanced medical training improves examination results among medical students and residents, according to research published in PLOS ONE.
“Ideally, medical training should be taking place at the patient’s bedside rather than in lecture halls,” said study author Daniel C. Baumgart, MD, PhD, of Charité Medical School at Humboldt-University of Berlin in Germany.
“Communication devices, such as tablet computers, digital assistants, and smartphones, make medical data and learning materials available anywhere and anytime. Therefore, our aim was to study the impact of a systematic integration of such devices into medical teaching and training.”
The researchers studied 55 final-year medical students and medical residents doing an inpatient service rotation. The subjects were assigned to receive a tablet personal computer (PC) with a custom multimedia education software package (n=24) or to a control group (n=31).
The multimedia package tested included the Mobile Medical Educator software package (developed in-house) as well as other multimedia learning materials, such as eBooks, eJournals, slide kits, podcasts, videos, animations, image data, and the American College of Physicians’ validated self-assessment software.
The participants had to complete MKSAP® (medical knowledge self-assessment program) exams at the beginning and the end of their training rotations. The final MKSAP score was the study’s primary endpoint.
The mean MKSAP score improved in the tablet PC group but not the control group. The final mean score was significantly higher in the tablet PC group than the control group—59 and 48, respectively (P<0.001).
When the researchers adjusted their analysis for subjects’ baseline score and potential confounders, the tablet PC group had, on average, 11% better MKSAP test results than the control group (P<0.001).
“We were able to show improvements in internal medicine exam results, which were independent of socio-demographic factors,” Dr Baumgart said. “Participant feedback was particularly positive in relation to an integrated, fully digitized workflow for clinical practice and training.”
Each added day of pediatric MRSA bacteremia upped complication risk 50%
Every additional day of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in hospitalized children was associated with a 50% increased risk of developing a complication, reported Rana F. Hamdy, MD, of Children’s National Health System, Washington, and her associates.
That was one of the findings of a study performed to determine the epidemiology, clinical outcomes, and risk factors for treatment failure in pediatric MRSA bacteremia. It took place in three hospitals, one each in Philadelphia, Baltimore, and Salt Lake City.
“This finding is in contrast to the epidemiology of MRSA bacteremia in adults, in whom bacteremia is more frequently attributed to catheter-related infections (31%-36%), endovascular infections (13%-15%), or an unknown source (15%-20%), and the durations of MRSA bacteremia are typically more prolonged (median duration of bacteremia is 8-9 days),” Dr. Hamdy and her associates wrote.
“Differences in the epidemiology of MRSA bacteremia between children and adults emphasize the need for dedicated pediatric studies to better understand the clinical characteristics and outcomes specific to children,” the researchers noted.
Musculoskeletal infections and endovascular infections were linked with treatment failure, possibly reflecting “the relatively higher burden of bacteria and/or decreased drug penetration into bone and endovascular infection sites,” the investigators said. Catheter-related infections were tied to reduced odds of treatment failure, “these episodes being localized to the catheter and therefore potentially less-invasive S. aureus infections.”
Mortality among these children with MRSA bacteremia was low, at 2%, but “nearly one-quarter of all patients experienced complications,” the study authors said (Pediatrics. 2017 May 5. doi: 10.1542/peds.2017-0183).
There was progression of infection in 7% of cases, and hematogenous complications or sequelae occurred in 23%. Twenty percent of children developed septic emboli or another metastatic focus of infection.
“This association between the duration of bacteremia and the development of complications has been previously reported among adults with S. aureus bacteremia,” Dr. Hamdy noted, “and provides important epidemiologic data that could inform decisions relating to the timing of additional imaging, such as echocardiograms, to identify metastatic foci.”
The children were treated with vancomycin, and some received additional anti-MRSA antibiotics. “Vancomycin trough concentrations or [minimum inhibitory concentrations] were not associated with treatment failure,” the investigators said. “Future studies to determine the appropriate vancomycin dose, duration, and approach to therapeutic drug monitoring are warranted to optimize patient outcomes.”
The National Institutes of Health funded the study. Dr. Hamdy and her associates disclosed they have no relevant financial relationships.
Every additional day of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in hospitalized children was associated with a 50% increased risk of developing a complication, reported Rana F. Hamdy, MD, of Children’s National Health System, Washington, and her associates.
That was one of the findings of a study performed to determine the epidemiology, clinical outcomes, and risk factors for treatment failure in pediatric MRSA bacteremia. It took place in three hospitals, one each in Philadelphia, Baltimore, and Salt Lake City.
“This finding is in contrast to the epidemiology of MRSA bacteremia in adults, in whom bacteremia is more frequently attributed to catheter-related infections (31%-36%), endovascular infections (13%-15%), or an unknown source (15%-20%), and the durations of MRSA bacteremia are typically more prolonged (median duration of bacteremia is 8-9 days),” Dr. Hamdy and her associates wrote.
“Differences in the epidemiology of MRSA bacteremia between children and adults emphasize the need for dedicated pediatric studies to better understand the clinical characteristics and outcomes specific to children,” the researchers noted.
Musculoskeletal infections and endovascular infections were linked with treatment failure, possibly reflecting “the relatively higher burden of bacteria and/or decreased drug penetration into bone and endovascular infection sites,” the investigators said. Catheter-related infections were tied to reduced odds of treatment failure, “these episodes being localized to the catheter and therefore potentially less-invasive S. aureus infections.”
Mortality among these children with MRSA bacteremia was low, at 2%, but “nearly one-quarter of all patients experienced complications,” the study authors said (Pediatrics. 2017 May 5. doi: 10.1542/peds.2017-0183).
There was progression of infection in 7% of cases, and hematogenous complications or sequelae occurred in 23%. Twenty percent of children developed septic emboli or another metastatic focus of infection.
“This association between the duration of bacteremia and the development of complications has been previously reported among adults with S. aureus bacteremia,” Dr. Hamdy noted, “and provides important epidemiologic data that could inform decisions relating to the timing of additional imaging, such as echocardiograms, to identify metastatic foci.”
The children were treated with vancomycin, and some received additional anti-MRSA antibiotics. “Vancomycin trough concentrations or [minimum inhibitory concentrations] were not associated with treatment failure,” the investigators said. “Future studies to determine the appropriate vancomycin dose, duration, and approach to therapeutic drug monitoring are warranted to optimize patient outcomes.”
The National Institutes of Health funded the study. Dr. Hamdy and her associates disclosed they have no relevant financial relationships.
Every additional day of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in hospitalized children was associated with a 50% increased risk of developing a complication, reported Rana F. Hamdy, MD, of Children’s National Health System, Washington, and her associates.
That was one of the findings of a study performed to determine the epidemiology, clinical outcomes, and risk factors for treatment failure in pediatric MRSA bacteremia. It took place in three hospitals, one each in Philadelphia, Baltimore, and Salt Lake City.
“This finding is in contrast to the epidemiology of MRSA bacteremia in adults, in whom bacteremia is more frequently attributed to catheter-related infections (31%-36%), endovascular infections (13%-15%), or an unknown source (15%-20%), and the durations of MRSA bacteremia are typically more prolonged (median duration of bacteremia is 8-9 days),” Dr. Hamdy and her associates wrote.
“Differences in the epidemiology of MRSA bacteremia between children and adults emphasize the need for dedicated pediatric studies to better understand the clinical characteristics and outcomes specific to children,” the researchers noted.
Musculoskeletal infections and endovascular infections were linked with treatment failure, possibly reflecting “the relatively higher burden of bacteria and/or decreased drug penetration into bone and endovascular infection sites,” the investigators said. Catheter-related infections were tied to reduced odds of treatment failure, “these episodes being localized to the catheter and therefore potentially less-invasive S. aureus infections.”
Mortality among these children with MRSA bacteremia was low, at 2%, but “nearly one-quarter of all patients experienced complications,” the study authors said (Pediatrics. 2017 May 5. doi: 10.1542/peds.2017-0183).
There was progression of infection in 7% of cases, and hematogenous complications or sequelae occurred in 23%. Twenty percent of children developed septic emboli or another metastatic focus of infection.
“This association between the duration of bacteremia and the development of complications has been previously reported among adults with S. aureus bacteremia,” Dr. Hamdy noted, “and provides important epidemiologic data that could inform decisions relating to the timing of additional imaging, such as echocardiograms, to identify metastatic foci.”
The children were treated with vancomycin, and some received additional anti-MRSA antibiotics. “Vancomycin trough concentrations or [minimum inhibitory concentrations] were not associated with treatment failure,” the investigators said. “Future studies to determine the appropriate vancomycin dose, duration, and approach to therapeutic drug monitoring are warranted to optimize patient outcomes.”
The National Institutes of Health funded the study. Dr. Hamdy and her associates disclosed they have no relevant financial relationships.
FROM PEDIATRICS
Key clinical point:
Major finding: The primary sources of infection were osteomyelitis (31%), catheter-related bloodstream infections (22%), and skin and soft tissue infections (16%); endocarditis occurred in only 2% – a different epidemiology than in adults.
Data source: A study of 174 hospitalized children (younger than 19 years) with MRSA bacteremia at three hospitals in different states.
Disclosures: The National Institutes of Health funded the study. Dr. Hamdy and her associates disclosed they have no relevant financial relationships.
When Can Exercise Supplant Surgery for Degenerative Meniscal Tears?
A 48-year-old man presents to your office for follow-up of right knee pain that has been bothering him for the past 12 months. He denies any trauma or inciting incident for the pain. On physical exam, he does not have crepitus but does have medial joint line tenderness of his right knee. An MRI shows a partial medial meniscal tear. Do you refer him to physical therapy (PT) or to orthopedics for arthroscopy and repair?
The meniscus—cartilage in the knee joint that provides support, stability, and lubrication to the joint during activity—can tear during a traumatic event or as a result of degeneration over time. Traumatic meniscal tears typically occur in those younger than 30 during sports (eg, basketball, soccer), whereas degenerative meniscal tears generally occur in patients ages 40 to 60.2,3 The annual incidence of all meniscal tears is 79 per 100,000.4 While some clinicians can diagnose traumatic meniscal tears based on history and physical examination, degenerative meniscal tears are more challenging and typically warrant an MRI for confirmation.3
Meniscal tears can be treated either conservatively, with supportive care and exercise, or surgically. Unfortunately, there are no national orthopedic guidelines available to help direct care. In one observational study, 95 of 117 patients (81.2%) were generally satisfied with surgical treatment at four-year follow-up; satisfaction was higher among those with a traumatic meniscal tear than in those with a degenerative tear.5
Two systematic reviews of surgery versus nonoperative management or sham therapies found no additional benefit of surgery for meniscal tears in a variety of patients with and without osteoarthritis.6,7 However, both studies were of only moderate quality, because of the number of patients in the nonoperative groups who ultimately underwent surgery. Neither of the studies directly compared surgery to nonoperative management.6,7Another investigation—a multicenter, randomized, double-blind, sham-controlled study conducted in Finland involving 1
Clinical practice recommendations devised from a vast systematic review of the literature recommend that the decision for surgery be based on patient-specific factors, such as symptoms, age, mechanism of tear, extent of damage, and occupational/social/activity needs.9
STUDY SUMMARY
Exercise is as good as surgery
The current superiority RCT compared exercise therapy to arthroscopic partial meniscectomy. Subjects (ages 35 to 60) presented to the orthopedic department of two hospitals in Norway with unilateral knee pain of more than two months’ duration and an MRI-delineated medial meniscal tear. They were included in the study only if they had radiographic evidence of minimal osteoarthritis (Kellgren-Lawrence classification grade ≤ 2). Exclusion criteria included acute trauma, locked knee, ligament injury, and knee surgery in the same knee within the previous two years.
The primary outcomes were change in patient-reported knee function (as determined by overall Knee injury and Osteoarthritis Outcome Score [KOOS] after two years) and thigh muscle strength at three months (as measured by physiotherapists). The researchers used four of the five KOOS subscales for this analysis: pain, other symptoms (swelling, grinding/noise from the joint, ability to straighten and bend), function in sports/recreation, and knee-related quality of life (QOL). The average score of each subscale was used.
Secondary outcomes included the five individual KOOS subscales (the four previously mentioned, plus activities of daily living [ADLs]), as well as thigh muscle strength and lower-extremity performance test results.
Methods. Testing personnel were blinded to group allocation; participants wore pants or neoprene sleeves to cover surgical scars. A total of 140 patients were randomized to either 12 weeks (24-36 sessions) of exercise therapy alone or a standardized arthroscopic partial meniscectomy; upon discharge, those in the latter group received written and oral encouragement to perform simple exercises at home, two to four times daily, to regain range of motion and reduce swelling.
Results. At two years, the overall mean improvement in KOOS4 score from baseline was similar between the exercise group and the meniscectomy group (25.3 pts vs 24.4 pts, respectively; mean difference [MD], 0.9). Additionally, muscle strength (measured as peak torque flexion and extension and total work flexion and extension) at both three and 12 months showed significant objective improvements favoring exercise therapy.
In the secondary analysis of the KOOS subscale scores, change from baseline was nonsignificant for four of the five (pain, ADL, sports/recreation, and QOL). Only the symptoms subscale had a significant difference favoring exercise therapy (MD, 5.3 pts); this was likely clinically insignificant on a grading scale of 0 to 100.
Of the patients allocated to exercise therapy alone, 19% crossed over and underwent surgery during the two-year study period.
WHAT’S NEW
Head-to-head comparison adds evidence
This is the first trial to directly compare exercise therapy to surgery in patients with meniscal tears. Interestingly, exercise therapy was as effective after a two-year follow-up period and was superior in the short term for thigh muscle strength.1
The results of this study build on those from the aforementioned smaller study conducted in Finland.8 In that study, both groups received instruction for the same graduated exercise plan. The researchers found that exercise was comparable to surgery for meniscal tears in patients with no osteoarthritis.
CAVEATS
What about more severe osteoarthritis?
This trial included patients with no to mild osteoarthritis in addition to their meniscal tear.1 It is unclear if the results would be maintained in those with more advanced disease. Additionally, 19% of patients crossed over from the exercise group to the surgery group, even though muscle strength improved. Therefore, education about the risks of surgery and the potential lack of benefit is important.
CHALLENGES TO IMPLEMENTATION
Cost and effort of PT
The cost of PT can be a barrier for patients who have adequate insurance coverage for surgery but inadequate coverage for PT. Additionally, exercise therapy requires significant and ongoing time and effort, which may deter those with busy lifestyles. Patients and clinicians may view surgery as an “easier” fix.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[4]:250-252).
1. Kise NJ, Risberg MA, Stensrud S, et al. Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients: randomised controlled trial with two year follow-up. BMJ. 2016;354:i3740.
2. Beals CT, Magnussen RA, Graham WC, et al. The prevalence of meniscal pathology in asymptomatic athletes. Sports Med. 2016;46:1517-1524.
3. Maffulli N, Longo UG, Campi S, et al. Meniscal tears. Open Access J Sports Med. 2010;1:45-54.
4. Peat G, Bergknut C, Frobell R, et al. Population-wide incidence estimates for soft tissue knee injuries presenting to healthcare in southern Sweden: data from the Skåne Healthcare Register. Arthritis Res Ther. 2014;16:R162.
5. Ghislain NA, Wei JN, Li YG. Study of the clinical outcome between traumatic and degenerative (non-traumatic) meniscal tears after arthroscopic surgery: a 4-years follow-up study. J Clin Diagn Res. 2016;10:RC01-RC04.
6. Khan M, Evaniew N, Bedi A, et al. Arthroscopic surgery for degenerative tears of the meniscus: a systematic review and meta-analysis. CMAJ. 2014;186:1057-1064.
7. Monk P, Garfjeld Roberts P, Palmer AJ, et al. The urgent need for evidence in arthroscopic meniscal surgery: a systematic review of the evidence for operative management of meniscal tears. Am J Sports Med. 2017;45:965-973.
8. Sihvonen R, Paavola M, Malmivaara A, et al; Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear. N Engl J Med. 2013;369:2515-2524.
9. Beaufils P, Hulet C, Dhénain M, et al. Clinical practice guidelines for the management of meniscal lesions and isolated lesions of the anterior cruciate ligament of the knee in adults. Orthop Traumatol Surg Res. 2009;95:437-442.
A 48-year-old man presents to your office for follow-up of right knee pain that has been bothering him for the past 12 months. He denies any trauma or inciting incident for the pain. On physical exam, he does not have crepitus but does have medial joint line tenderness of his right knee. An MRI shows a partial medial meniscal tear. Do you refer him to physical therapy (PT) or to orthopedics for arthroscopy and repair?
The meniscus—cartilage in the knee joint that provides support, stability, and lubrication to the joint during activity—can tear during a traumatic event or as a result of degeneration over time. Traumatic meniscal tears typically occur in those younger than 30 during sports (eg, basketball, soccer), whereas degenerative meniscal tears generally occur in patients ages 40 to 60.2,3 The annual incidence of all meniscal tears is 79 per 100,000.4 While some clinicians can diagnose traumatic meniscal tears based on history and physical examination, degenerative meniscal tears are more challenging and typically warrant an MRI for confirmation.3
Meniscal tears can be treated either conservatively, with supportive care and exercise, or surgically. Unfortunately, there are no national orthopedic guidelines available to help direct care. In one observational study, 95 of 117 patients (81.2%) were generally satisfied with surgical treatment at four-year follow-up; satisfaction was higher among those with a traumatic meniscal tear than in those with a degenerative tear.5
Two systematic reviews of surgery versus nonoperative management or sham therapies found no additional benefit of surgery for meniscal tears in a variety of patients with and without osteoarthritis.6,7 However, both studies were of only moderate quality, because of the number of patients in the nonoperative groups who ultimately underwent surgery. Neither of the studies directly compared surgery to nonoperative management.6,7Another investigation—a multicenter, randomized, double-blind, sham-controlled study conducted in Finland involving 1
Clinical practice recommendations devised from a vast systematic review of the literature recommend that the decision for surgery be based on patient-specific factors, such as symptoms, age, mechanism of tear, extent of damage, and occupational/social/activity needs.9
STUDY SUMMARY
Exercise is as good as surgery
The current superiority RCT compared exercise therapy to arthroscopic partial meniscectomy. Subjects (ages 35 to 60) presented to the orthopedic department of two hospitals in Norway with unilateral knee pain of more than two months’ duration and an MRI-delineated medial meniscal tear. They were included in the study only if they had radiographic evidence of minimal osteoarthritis (Kellgren-Lawrence classification grade ≤ 2). Exclusion criteria included acute trauma, locked knee, ligament injury, and knee surgery in the same knee within the previous two years.
The primary outcomes were change in patient-reported knee function (as determined by overall Knee injury and Osteoarthritis Outcome Score [KOOS] after two years) and thigh muscle strength at three months (as measured by physiotherapists). The researchers used four of the five KOOS subscales for this analysis: pain, other symptoms (swelling, grinding/noise from the joint, ability to straighten and bend), function in sports/recreation, and knee-related quality of life (QOL). The average score of each subscale was used.
Secondary outcomes included the five individual KOOS subscales (the four previously mentioned, plus activities of daily living [ADLs]), as well as thigh muscle strength and lower-extremity performance test results.
Methods. Testing personnel were blinded to group allocation; participants wore pants or neoprene sleeves to cover surgical scars. A total of 140 patients were randomized to either 12 weeks (24-36 sessions) of exercise therapy alone or a standardized arthroscopic partial meniscectomy; upon discharge, those in the latter group received written and oral encouragement to perform simple exercises at home, two to four times daily, to regain range of motion and reduce swelling.
Results. At two years, the overall mean improvement in KOOS4 score from baseline was similar between the exercise group and the meniscectomy group (25.3 pts vs 24.4 pts, respectively; mean difference [MD], 0.9). Additionally, muscle strength (measured as peak torque flexion and extension and total work flexion and extension) at both three and 12 months showed significant objective improvements favoring exercise therapy.
In the secondary analysis of the KOOS subscale scores, change from baseline was nonsignificant for four of the five (pain, ADL, sports/recreation, and QOL). Only the symptoms subscale had a significant difference favoring exercise therapy (MD, 5.3 pts); this was likely clinically insignificant on a grading scale of 0 to 100.
Of the patients allocated to exercise therapy alone, 19% crossed over and underwent surgery during the two-year study period.
WHAT’S NEW
Head-to-head comparison adds evidence
This is the first trial to directly compare exercise therapy to surgery in patients with meniscal tears. Interestingly, exercise therapy was as effective after a two-year follow-up period and was superior in the short term for thigh muscle strength.1
The results of this study build on those from the aforementioned smaller study conducted in Finland.8 In that study, both groups received instruction for the same graduated exercise plan. The researchers found that exercise was comparable to surgery for meniscal tears in patients with no osteoarthritis.
CAVEATS
What about more severe osteoarthritis?
This trial included patients with no to mild osteoarthritis in addition to their meniscal tear.1 It is unclear if the results would be maintained in those with more advanced disease. Additionally, 19% of patients crossed over from the exercise group to the surgery group, even though muscle strength improved. Therefore, education about the risks of surgery and the potential lack of benefit is important.
CHALLENGES TO IMPLEMENTATION
Cost and effort of PT
The cost of PT can be a barrier for patients who have adequate insurance coverage for surgery but inadequate coverage for PT. Additionally, exercise therapy requires significant and ongoing time and effort, which may deter those with busy lifestyles. Patients and clinicians may view surgery as an “easier” fix.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[4]:250-252).
A 48-year-old man presents to your office for follow-up of right knee pain that has been bothering him for the past 12 months. He denies any trauma or inciting incident for the pain. On physical exam, he does not have crepitus but does have medial joint line tenderness of his right knee. An MRI shows a partial medial meniscal tear. Do you refer him to physical therapy (PT) or to orthopedics for arthroscopy and repair?
The meniscus—cartilage in the knee joint that provides support, stability, and lubrication to the joint during activity—can tear during a traumatic event or as a result of degeneration over time. Traumatic meniscal tears typically occur in those younger than 30 during sports (eg, basketball, soccer), whereas degenerative meniscal tears generally occur in patients ages 40 to 60.2,3 The annual incidence of all meniscal tears is 79 per 100,000.4 While some clinicians can diagnose traumatic meniscal tears based on history and physical examination, degenerative meniscal tears are more challenging and typically warrant an MRI for confirmation.3
Meniscal tears can be treated either conservatively, with supportive care and exercise, or surgically. Unfortunately, there are no national orthopedic guidelines available to help direct care. In one observational study, 95 of 117 patients (81.2%) were generally satisfied with surgical treatment at four-year follow-up; satisfaction was higher among those with a traumatic meniscal tear than in those with a degenerative tear.5
Two systematic reviews of surgery versus nonoperative management or sham therapies found no additional benefit of surgery for meniscal tears in a variety of patients with and without osteoarthritis.6,7 However, both studies were of only moderate quality, because of the number of patients in the nonoperative groups who ultimately underwent surgery. Neither of the studies directly compared surgery to nonoperative management.6,7Another investigation—a multicenter, randomized, double-blind, sham-controlled study conducted in Finland involving 1
Clinical practice recommendations devised from a vast systematic review of the literature recommend that the decision for surgery be based on patient-specific factors, such as symptoms, age, mechanism of tear, extent of damage, and occupational/social/activity needs.9
STUDY SUMMARY
Exercise is as good as surgery
The current superiority RCT compared exercise therapy to arthroscopic partial meniscectomy. Subjects (ages 35 to 60) presented to the orthopedic department of two hospitals in Norway with unilateral knee pain of more than two months’ duration and an MRI-delineated medial meniscal tear. They were included in the study only if they had radiographic evidence of minimal osteoarthritis (Kellgren-Lawrence classification grade ≤ 2). Exclusion criteria included acute trauma, locked knee, ligament injury, and knee surgery in the same knee within the previous two years.
The primary outcomes were change in patient-reported knee function (as determined by overall Knee injury and Osteoarthritis Outcome Score [KOOS] after two years) and thigh muscle strength at three months (as measured by physiotherapists). The researchers used four of the five KOOS subscales for this analysis: pain, other symptoms (swelling, grinding/noise from the joint, ability to straighten and bend), function in sports/recreation, and knee-related quality of life (QOL). The average score of each subscale was used.
Secondary outcomes included the five individual KOOS subscales (the four previously mentioned, plus activities of daily living [ADLs]), as well as thigh muscle strength and lower-extremity performance test results.
Methods. Testing personnel were blinded to group allocation; participants wore pants or neoprene sleeves to cover surgical scars. A total of 140 patients were randomized to either 12 weeks (24-36 sessions) of exercise therapy alone or a standardized arthroscopic partial meniscectomy; upon discharge, those in the latter group received written and oral encouragement to perform simple exercises at home, two to four times daily, to regain range of motion and reduce swelling.
Results. At two years, the overall mean improvement in KOOS4 score from baseline was similar between the exercise group and the meniscectomy group (25.3 pts vs 24.4 pts, respectively; mean difference [MD], 0.9). Additionally, muscle strength (measured as peak torque flexion and extension and total work flexion and extension) at both three and 12 months showed significant objective improvements favoring exercise therapy.
In the secondary analysis of the KOOS subscale scores, change from baseline was nonsignificant for four of the five (pain, ADL, sports/recreation, and QOL). Only the symptoms subscale had a significant difference favoring exercise therapy (MD, 5.3 pts); this was likely clinically insignificant on a grading scale of 0 to 100.
Of the patients allocated to exercise therapy alone, 19% crossed over and underwent surgery during the two-year study period.
WHAT’S NEW
Head-to-head comparison adds evidence
This is the first trial to directly compare exercise therapy to surgery in patients with meniscal tears. Interestingly, exercise therapy was as effective after a two-year follow-up period and was superior in the short term for thigh muscle strength.1
The results of this study build on those from the aforementioned smaller study conducted in Finland.8 In that study, both groups received instruction for the same graduated exercise plan. The researchers found that exercise was comparable to surgery for meniscal tears in patients with no osteoarthritis.
CAVEATS
What about more severe osteoarthritis?
This trial included patients with no to mild osteoarthritis in addition to their meniscal tear.1 It is unclear if the results would be maintained in those with more advanced disease. Additionally, 19% of patients crossed over from the exercise group to the surgery group, even though muscle strength improved. Therefore, education about the risks of surgery and the potential lack of benefit is important.
CHALLENGES TO IMPLEMENTATION
Cost and effort of PT
The cost of PT can be a barrier for patients who have adequate insurance coverage for surgery but inadequate coverage for PT. Additionally, exercise therapy requires significant and ongoing time and effort, which may deter those with busy lifestyles. Patients and clinicians may view surgery as an “easier” fix.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[4]:250-252).
1. Kise NJ, Risberg MA, Stensrud S, et al. Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients: randomised controlled trial with two year follow-up. BMJ. 2016;354:i3740.
2. Beals CT, Magnussen RA, Graham WC, et al. The prevalence of meniscal pathology in asymptomatic athletes. Sports Med. 2016;46:1517-1524.
3. Maffulli N, Longo UG, Campi S, et al. Meniscal tears. Open Access J Sports Med. 2010;1:45-54.
4. Peat G, Bergknut C, Frobell R, et al. Population-wide incidence estimates for soft tissue knee injuries presenting to healthcare in southern Sweden: data from the Skåne Healthcare Register. Arthritis Res Ther. 2014;16:R162.
5. Ghislain NA, Wei JN, Li YG. Study of the clinical outcome between traumatic and degenerative (non-traumatic) meniscal tears after arthroscopic surgery: a 4-years follow-up study. J Clin Diagn Res. 2016;10:RC01-RC04.
6. Khan M, Evaniew N, Bedi A, et al. Arthroscopic surgery for degenerative tears of the meniscus: a systematic review and meta-analysis. CMAJ. 2014;186:1057-1064.
7. Monk P, Garfjeld Roberts P, Palmer AJ, et al. The urgent need for evidence in arthroscopic meniscal surgery: a systematic review of the evidence for operative management of meniscal tears. Am J Sports Med. 2017;45:965-973.
8. Sihvonen R, Paavola M, Malmivaara A, et al; Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear. N Engl J Med. 2013;369:2515-2524.
9. Beaufils P, Hulet C, Dhénain M, et al. Clinical practice guidelines for the management of meniscal lesions and isolated lesions of the anterior cruciate ligament of the knee in adults. Orthop Traumatol Surg Res. 2009;95:437-442.
1. Kise NJ, Risberg MA, Stensrud S, et al. Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients: randomised controlled trial with two year follow-up. BMJ. 2016;354:i3740.
2. Beals CT, Magnussen RA, Graham WC, et al. The prevalence of meniscal pathology in asymptomatic athletes. Sports Med. 2016;46:1517-1524.
3. Maffulli N, Longo UG, Campi S, et al. Meniscal tears. Open Access J Sports Med. 2010;1:45-54.
4. Peat G, Bergknut C, Frobell R, et al. Population-wide incidence estimates for soft tissue knee injuries presenting to healthcare in southern Sweden: data from the Skåne Healthcare Register. Arthritis Res Ther. 2014;16:R162.
5. Ghislain NA, Wei JN, Li YG. Study of the clinical outcome between traumatic and degenerative (non-traumatic) meniscal tears after arthroscopic surgery: a 4-years follow-up study. J Clin Diagn Res. 2016;10:RC01-RC04.
6. Khan M, Evaniew N, Bedi A, et al. Arthroscopic surgery for degenerative tears of the meniscus: a systematic review and meta-analysis. CMAJ. 2014;186:1057-1064.
7. Monk P, Garfjeld Roberts P, Palmer AJ, et al. The urgent need for evidence in arthroscopic meniscal surgery: a systematic review of the evidence for operative management of meniscal tears. Am J Sports Med. 2017;45:965-973.
8. Sihvonen R, Paavola M, Malmivaara A, et al; Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear. N Engl J Med. 2013;369:2515-2524.
9. Beaufils P, Hulet C, Dhénain M, et al. Clinical practice guidelines for the management of meniscal lesions and isolated lesions of the anterior cruciate ligament of the knee in adults. Orthop Traumatol Surg Res. 2009;95:437-442.
Perioperative pharmacological thromboprophylaxis in patients with cancer: a systematic review and meta-analysis
CLINICAL QUESTION: What are the benefits and harms of perioperative pharmacological thromboprophylaxis in cancer patients undergoing surgery?
STUDY DESIGN: Systematic review and meta-analysis.
SYNOPSIS: Thirty-nine trials were deemed eligible for inclusion in the meta-analysis. Twenty-five of these were prospective and 14 were retrospective. The overall incidence of deep venous thrombosis (DVT) and pulmonary embolism was 0.9% (across 20 studies) and 0.3% (across 19 studies), respectively. Pharmacologic prophylaxis overall reduced DVT incidence (0.5% vs. 1.2%; relative risk, 0.51; P = .03). Subgroup analysis demonstrated this was significant for abdominal/pelvic surgeries and with low molecular weight heparin. Six studies compared duration of standard prophylaxis (10 days) with extended prophylaxis (4 weeks), with a lower VTE rate in the extended group. Bleeding events were noted in 13 studies and pharmacologic prophylaxis significantly increased bleeding risk (2.7% vs. 8%; RR, 2.51; P less than .0001).
BOTTOM LINE: Perioperative pharmacologic prophylaxis reduces DVT risk in patients with cancer, with greatest risk reduction seen in patients undergoing abdominal/pelvic surgeries. This comes at the cost of increased bleeding complications.
CITATIONS: Guo Q, Huang B, Zhao J, et al. Perioperative pharmacological thromboprophylaxis in patients with cancer: a systematic review and meta-analysis. Ann Surg. 2016 Nov. doi: 10.1097/SLA.0000000000002074.
Dr. Patil is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: What are the benefits and harms of perioperative pharmacological thromboprophylaxis in cancer patients undergoing surgery?
STUDY DESIGN: Systematic review and meta-analysis.
SYNOPSIS: Thirty-nine trials were deemed eligible for inclusion in the meta-analysis. Twenty-five of these were prospective and 14 were retrospective. The overall incidence of deep venous thrombosis (DVT) and pulmonary embolism was 0.9% (across 20 studies) and 0.3% (across 19 studies), respectively. Pharmacologic prophylaxis overall reduced DVT incidence (0.5% vs. 1.2%; relative risk, 0.51; P = .03). Subgroup analysis demonstrated this was significant for abdominal/pelvic surgeries and with low molecular weight heparin. Six studies compared duration of standard prophylaxis (10 days) with extended prophylaxis (4 weeks), with a lower VTE rate in the extended group. Bleeding events were noted in 13 studies and pharmacologic prophylaxis significantly increased bleeding risk (2.7% vs. 8%; RR, 2.51; P less than .0001).
BOTTOM LINE: Perioperative pharmacologic prophylaxis reduces DVT risk in patients with cancer, with greatest risk reduction seen in patients undergoing abdominal/pelvic surgeries. This comes at the cost of increased bleeding complications.
CITATIONS: Guo Q, Huang B, Zhao J, et al. Perioperative pharmacological thromboprophylaxis in patients with cancer: a systematic review and meta-analysis. Ann Surg. 2016 Nov. doi: 10.1097/SLA.0000000000002074.
Dr. Patil is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: What are the benefits and harms of perioperative pharmacological thromboprophylaxis in cancer patients undergoing surgery?
STUDY DESIGN: Systematic review and meta-analysis.
SYNOPSIS: Thirty-nine trials were deemed eligible for inclusion in the meta-analysis. Twenty-five of these were prospective and 14 were retrospective. The overall incidence of deep venous thrombosis (DVT) and pulmonary embolism was 0.9% (across 20 studies) and 0.3% (across 19 studies), respectively. Pharmacologic prophylaxis overall reduced DVT incidence (0.5% vs. 1.2%; relative risk, 0.51; P = .03). Subgroup analysis demonstrated this was significant for abdominal/pelvic surgeries and with low molecular weight heparin. Six studies compared duration of standard prophylaxis (10 days) with extended prophylaxis (4 weeks), with a lower VTE rate in the extended group. Bleeding events were noted in 13 studies and pharmacologic prophylaxis significantly increased bleeding risk (2.7% vs. 8%; RR, 2.51; P less than .0001).
BOTTOM LINE: Perioperative pharmacologic prophylaxis reduces DVT risk in patients with cancer, with greatest risk reduction seen in patients undergoing abdominal/pelvic surgeries. This comes at the cost of increased bleeding complications.
CITATIONS: Guo Q, Huang B, Zhao J, et al. Perioperative pharmacological thromboprophylaxis in patients with cancer: a systematic review and meta-analysis. Ann Surg. 2016 Nov. doi: 10.1097/SLA.0000000000002074.
Dr. Patil is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
Readmission rates after passage of the hospital readmissions reduction program
CLINICAL QUESTION: Did hospitals receiving the highest penalties for readmissions have accelerated improvement in this metric after passage of Medicare Hospital Readmissions Reduction Program (HRRP)?
BACKGROUND: Medicare passed the HRRP to incentivize reductions in readmission rates. The impact of penalties on relative hospital improvement rates remains unknown.
SETTING: Query of national Medicare Provider Analysis and Review files.
SYNOPSIS: 2,868 hospitals were identified as candidates for analysis and were stratified into four risk groups based on penalty size under HRRP: highest-performing, average-performing, low-performing, and lowest-performing. The primary outcomes were hospital-specific, 30-day, all-cause risk-standardized readmission rates (RSRRs) for patients discharged with acute MI, HF, or pneumonia. The investigators separated data into a pre-law period and post-law period. They fitted a logistic regression model to pre-law RSRRs and developed a piecewise linear model on post-law RSRRs with pre-law data as the dependent variable. All hospital groups had reductions in RSRRs, with the lowest quartile demonstrating greatest improvement.
BOTTOM LINE: HRRP has resulted in reductions in RSRRs with greatest improvement in hospitals with lowest pre-law performance.
CITATIONS: Wasfy JH, Zigler CM, Choirat C, et al. Readmission rates after passage of the hospital readmissions reduction program: a pre-post analysis. Ann Intern Med. 2017 Mar;166(5):324-31.
Dr. Patil is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: Did hospitals receiving the highest penalties for readmissions have accelerated improvement in this metric after passage of Medicare Hospital Readmissions Reduction Program (HRRP)?
BACKGROUND: Medicare passed the HRRP to incentivize reductions in readmission rates. The impact of penalties on relative hospital improvement rates remains unknown.
SETTING: Query of national Medicare Provider Analysis and Review files.
SYNOPSIS: 2,868 hospitals were identified as candidates for analysis and were stratified into four risk groups based on penalty size under HRRP: highest-performing, average-performing, low-performing, and lowest-performing. The primary outcomes were hospital-specific, 30-day, all-cause risk-standardized readmission rates (RSRRs) for patients discharged with acute MI, HF, or pneumonia. The investigators separated data into a pre-law period and post-law period. They fitted a logistic regression model to pre-law RSRRs and developed a piecewise linear model on post-law RSRRs with pre-law data as the dependent variable. All hospital groups had reductions in RSRRs, with the lowest quartile demonstrating greatest improvement.
BOTTOM LINE: HRRP has resulted in reductions in RSRRs with greatest improvement in hospitals with lowest pre-law performance.
CITATIONS: Wasfy JH, Zigler CM, Choirat C, et al. Readmission rates after passage of the hospital readmissions reduction program: a pre-post analysis. Ann Intern Med. 2017 Mar;166(5):324-31.
Dr. Patil is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: Did hospitals receiving the highest penalties for readmissions have accelerated improvement in this metric after passage of Medicare Hospital Readmissions Reduction Program (HRRP)?
BACKGROUND: Medicare passed the HRRP to incentivize reductions in readmission rates. The impact of penalties on relative hospital improvement rates remains unknown.
SETTING: Query of national Medicare Provider Analysis and Review files.
SYNOPSIS: 2,868 hospitals were identified as candidates for analysis and were stratified into four risk groups based on penalty size under HRRP: highest-performing, average-performing, low-performing, and lowest-performing. The primary outcomes were hospital-specific, 30-day, all-cause risk-standardized readmission rates (RSRRs) for patients discharged with acute MI, HF, or pneumonia. The investigators separated data into a pre-law period and post-law period. They fitted a logistic regression model to pre-law RSRRs and developed a piecewise linear model on post-law RSRRs with pre-law data as the dependent variable. All hospital groups had reductions in RSRRs, with the lowest quartile demonstrating greatest improvement.
BOTTOM LINE: HRRP has resulted in reductions in RSRRs with greatest improvement in hospitals with lowest pre-law performance.
CITATIONS: Wasfy JH, Zigler CM, Choirat C, et al. Readmission rates after passage of the hospital readmissions reduction program: a pre-post analysis. Ann Intern Med. 2017 Mar;166(5):324-31.
Dr. Patil is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
Assessment of goals of care in nursing home reduces hospitalization for patients with dementia
CLINICAL QUESTION: For patients with advanced dementia, does a goals-of-care intervention improve communication and care outcomes?
STUDY DESIGN: Single-blind cluster randomized trial.
SETTING: Twenty-two nursing homes in North Carolina.
SYNOPSIS: Three hundred and two patient/families enrolled. Intervention included video and print decision aids followed by a structured goals of care discussion with trained nursing home staff. Quality of communication results, the primary outcome, at 3 months were mixed. Family perception of communication with nursing home staff was better in the intervention. Family–health care provider concordance on primary goal of care and treatment consistent with preferences were not significantly different. By the end of the study at 9 months there was no difference in symptom control but some secondary outcomes were encouraging including greater completion of MOST advanced directives (35% vs. 16%; P = .05) and half as many hospital transfers. Multiple comparisons merits future verification of secondary outcome findings.
BOTTOM LINE: Goals of care discussions for patients with advanced dementia appears to reduce hospitalizations.
CITATIONS: Hanson LC, Zimmerman S, Song MK, et al. Effect of the goals of care intervention for advanced dementia: a randomized clinical trial. JAMA Intern Med. 2017 Jan;177:24-31.
Dr. Cumbler is the associate chief of hospital medicine, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: For patients with advanced dementia, does a goals-of-care intervention improve communication and care outcomes?
STUDY DESIGN: Single-blind cluster randomized trial.
SETTING: Twenty-two nursing homes in North Carolina.
SYNOPSIS: Three hundred and two patient/families enrolled. Intervention included video and print decision aids followed by a structured goals of care discussion with trained nursing home staff. Quality of communication results, the primary outcome, at 3 months were mixed. Family perception of communication with nursing home staff was better in the intervention. Family–health care provider concordance on primary goal of care and treatment consistent with preferences were not significantly different. By the end of the study at 9 months there was no difference in symptom control but some secondary outcomes were encouraging including greater completion of MOST advanced directives (35% vs. 16%; P = .05) and half as many hospital transfers. Multiple comparisons merits future verification of secondary outcome findings.
BOTTOM LINE: Goals of care discussions for patients with advanced dementia appears to reduce hospitalizations.
CITATIONS: Hanson LC, Zimmerman S, Song MK, et al. Effect of the goals of care intervention for advanced dementia: a randomized clinical trial. JAMA Intern Med. 2017 Jan;177:24-31.
Dr. Cumbler is the associate chief of hospital medicine, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: For patients with advanced dementia, does a goals-of-care intervention improve communication and care outcomes?
STUDY DESIGN: Single-blind cluster randomized trial.
SETTING: Twenty-two nursing homes in North Carolina.
SYNOPSIS: Three hundred and two patient/families enrolled. Intervention included video and print decision aids followed by a structured goals of care discussion with trained nursing home staff. Quality of communication results, the primary outcome, at 3 months were mixed. Family perception of communication with nursing home staff was better in the intervention. Family–health care provider concordance on primary goal of care and treatment consistent with preferences were not significantly different. By the end of the study at 9 months there was no difference in symptom control but some secondary outcomes were encouraging including greater completion of MOST advanced directives (35% vs. 16%; P = .05) and half as many hospital transfers. Multiple comparisons merits future verification of secondary outcome findings.
BOTTOM LINE: Goals of care discussions for patients with advanced dementia appears to reduce hospitalizations.
CITATIONS: Hanson LC, Zimmerman S, Song MK, et al. Effect of the goals of care intervention for advanced dementia: a randomized clinical trial. JAMA Intern Med. 2017 Jan;177:24-31.
Dr. Cumbler is the associate chief of hospital medicine, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
Daratumumab, elotuzumab eyed for initial treatment of myeloma
The emerging role for immunotherapies as an essential component of multiple myeloma therapy is examined in a review article in Leukemia by Cyrille Touzeau, MD, and his colleagues.
The reviewers detail research examining a string of monoclonal antibodies that fell short in earlier evaluations. They focus on the two approved agents that target CD38 (daratumumab) and SLAMF7 (elotuzumab) and have succeeded in combination therapies for patients with relapsed myeloma. These two antibodies, and other immunotherapy possibilities in the pipeline, are expected to have a strong impact on treatment modalities and outcomes in patients with multiple myeloma, including transplant eligible and elderly patients, Dr. Touzeau, of the service d’hématologie clinique, Nantes, France, and his fellow researchers wrote.
In two phase III randomized studies, ELO 1 (NCT01891643) and ELOQUENT 1 (NCT01335399), previously untreated myeloma patients are receiving lenalidomide/dexamethasone with or without elotuzumab.
In another ongoing trial, elotuzumab is being evaluated in combination with the anti-KIR antibody lirilumab and the anti-CD137 antibody urelumab (NCT02252263). Elotuzumab also is being studied in combination with lenalidomide as maintenance after high-dose therapy (NCT02420860).
Additionally, elotuzumab in combination with pomalidomide-dexamethasone is being examined for relapsed myeloma in an ongoing phase II randomized trial (NCT02654132). SLAMF7 is also being evaluated as a target for immunoconjugate therapy, with an ongoing trial of an auristatin E conjugate (ABBV-838) in patients with relapsed or refractory disease (NCT02462525), the reviewers note.
Daratumumab is being examined in combination with VTD [bortezomib (Velcade)/thalidomide/dexamethasone] as induction therapy and for its role as maintenance after high-dose therapy, among previously untreated transplant-eligible myeloma patients in the phase III randomized Cassiopeia study (NCT02541383).
In patients not eligible for transplant, the phase III randomized trial, MAIA, is evaluating the addition of daratumumab to lenalidomide-dexamethasone (NCT02252172). In high-risk smoldering myeloma, daratumumab is being evaluated in the phase III randomized CENTAURUS trial (NCT02316106). PAVO is a phase 1b study of the subcutaneous administration of daratumumab (NCT02519452). Preliminary results determined that the fixed subcutaneous dose of 1800 mg was consistent with the 16 mg/kg IV dose in terms of pharmacokinetics.
Dr. Touzeau declared no conflicts of interest. His coauthors participate in advisory boards and receive honoraria from several drug makers including the makers of immunotherapies.
[email protected]
On Twitter @maryjodales
The emerging role for immunotherapies as an essential component of multiple myeloma therapy is examined in a review article in Leukemia by Cyrille Touzeau, MD, and his colleagues.
The reviewers detail research examining a string of monoclonal antibodies that fell short in earlier evaluations. They focus on the two approved agents that target CD38 (daratumumab) and SLAMF7 (elotuzumab) and have succeeded in combination therapies for patients with relapsed myeloma. These two antibodies, and other immunotherapy possibilities in the pipeline, are expected to have a strong impact on treatment modalities and outcomes in patients with multiple myeloma, including transplant eligible and elderly patients, Dr. Touzeau, of the service d’hématologie clinique, Nantes, France, and his fellow researchers wrote.
In two phase III randomized studies, ELO 1 (NCT01891643) and ELOQUENT 1 (NCT01335399), previously untreated myeloma patients are receiving lenalidomide/dexamethasone with or without elotuzumab.
In another ongoing trial, elotuzumab is being evaluated in combination with the anti-KIR antibody lirilumab and the anti-CD137 antibody urelumab (NCT02252263). Elotuzumab also is being studied in combination with lenalidomide as maintenance after high-dose therapy (NCT02420860).
Additionally, elotuzumab in combination with pomalidomide-dexamethasone is being examined for relapsed myeloma in an ongoing phase II randomized trial (NCT02654132). SLAMF7 is also being evaluated as a target for immunoconjugate therapy, with an ongoing trial of an auristatin E conjugate (ABBV-838) in patients with relapsed or refractory disease (NCT02462525), the reviewers note.
Daratumumab is being examined in combination with VTD [bortezomib (Velcade)/thalidomide/dexamethasone] as induction therapy and for its role as maintenance after high-dose therapy, among previously untreated transplant-eligible myeloma patients in the phase III randomized Cassiopeia study (NCT02541383).
In patients not eligible for transplant, the phase III randomized trial, MAIA, is evaluating the addition of daratumumab to lenalidomide-dexamethasone (NCT02252172). In high-risk smoldering myeloma, daratumumab is being evaluated in the phase III randomized CENTAURUS trial (NCT02316106). PAVO is a phase 1b study of the subcutaneous administration of daratumumab (NCT02519452). Preliminary results determined that the fixed subcutaneous dose of 1800 mg was consistent with the 16 mg/kg IV dose in terms of pharmacokinetics.
Dr. Touzeau declared no conflicts of interest. His coauthors participate in advisory boards and receive honoraria from several drug makers including the makers of immunotherapies.
[email protected]
On Twitter @maryjodales
The emerging role for immunotherapies as an essential component of multiple myeloma therapy is examined in a review article in Leukemia by Cyrille Touzeau, MD, and his colleagues.
The reviewers detail research examining a string of monoclonal antibodies that fell short in earlier evaluations. They focus on the two approved agents that target CD38 (daratumumab) and SLAMF7 (elotuzumab) and have succeeded in combination therapies for patients with relapsed myeloma. These two antibodies, and other immunotherapy possibilities in the pipeline, are expected to have a strong impact on treatment modalities and outcomes in patients with multiple myeloma, including transplant eligible and elderly patients, Dr. Touzeau, of the service d’hématologie clinique, Nantes, France, and his fellow researchers wrote.
In two phase III randomized studies, ELO 1 (NCT01891643) and ELOQUENT 1 (NCT01335399), previously untreated myeloma patients are receiving lenalidomide/dexamethasone with or without elotuzumab.
In another ongoing trial, elotuzumab is being evaluated in combination with the anti-KIR antibody lirilumab and the anti-CD137 antibody urelumab (NCT02252263). Elotuzumab also is being studied in combination with lenalidomide as maintenance after high-dose therapy (NCT02420860).
Additionally, elotuzumab in combination with pomalidomide-dexamethasone is being examined for relapsed myeloma in an ongoing phase II randomized trial (NCT02654132). SLAMF7 is also being evaluated as a target for immunoconjugate therapy, with an ongoing trial of an auristatin E conjugate (ABBV-838) in patients with relapsed or refractory disease (NCT02462525), the reviewers note.
Daratumumab is being examined in combination with VTD [bortezomib (Velcade)/thalidomide/dexamethasone] as induction therapy and for its role as maintenance after high-dose therapy, among previously untreated transplant-eligible myeloma patients in the phase III randomized Cassiopeia study (NCT02541383).
In patients not eligible for transplant, the phase III randomized trial, MAIA, is evaluating the addition of daratumumab to lenalidomide-dexamethasone (NCT02252172). In high-risk smoldering myeloma, daratumumab is being evaluated in the phase III randomized CENTAURUS trial (NCT02316106). PAVO is a phase 1b study of the subcutaneous administration of daratumumab (NCT02519452). Preliminary results determined that the fixed subcutaneous dose of 1800 mg was consistent with the 16 mg/kg IV dose in terms of pharmacokinetics.
Dr. Touzeau declared no conflicts of interest. His coauthors participate in advisory boards and receive honoraria from several drug makers including the makers of immunotherapies.
[email protected]
On Twitter @maryjodales
FROM LEUKEMIA
Two doses HPV vaccine are as good as three against genital warts
Receiving two doses of human papillomavirus (HPV) vaccine at 5-month intervals or longer appears to provide similar protection against genital warts as three doses among girls initiating the series before age 15 years, reported Rebecca B. Perkins, MD, of Boston University, and her associates.
Of 387,906 adolescent females, 8% received 1 dose of HPV vaccine, 9% received 2 doses, 31% received 3 doses, and 52% remained unvaccinated. The mean age of the girls in the study was 15 years, and average length of follow-up was 6 years. The girls were aged 9-18 years on Jan.1, 2007, and the exposure period began at that time for unvaccinated girls or on the date of the last HPV vaccine injection for those receiving the vaccine. Among girls receiving more than 1 dose, 60% received their second dose within 3 months of their first dose (on time), and 47% received their third dose within 5 months of their second dose.
“Although reductions in genital warts are an important early marker of vaccine effectiveness, reductions in cervical dysplasia and cancers are far more important vaccine-related outcomes,” Dr. Perkins and her associates said. “Human papillomavirus vaccine protection must last many years to provide adequate cancer protection, therefore ongoing studies are paramount,” they noted.
The study used data from the Truven Health Analytics MarketScan Commercial Claims Database, covering enrollees and dependents from about half of provider-sponsored U.S. health insurance plans.
Read more at (Sex Transm Dis. 2017 Jun. doi: 10.1097/OLQ.0000000000000615).
Receiving two doses of human papillomavirus (HPV) vaccine at 5-month intervals or longer appears to provide similar protection against genital warts as three doses among girls initiating the series before age 15 years, reported Rebecca B. Perkins, MD, of Boston University, and her associates.
Of 387,906 adolescent females, 8% received 1 dose of HPV vaccine, 9% received 2 doses, 31% received 3 doses, and 52% remained unvaccinated. The mean age of the girls in the study was 15 years, and average length of follow-up was 6 years. The girls were aged 9-18 years on Jan.1, 2007, and the exposure period began at that time for unvaccinated girls or on the date of the last HPV vaccine injection for those receiving the vaccine. Among girls receiving more than 1 dose, 60% received their second dose within 3 months of their first dose (on time), and 47% received their third dose within 5 months of their second dose.
“Although reductions in genital warts are an important early marker of vaccine effectiveness, reductions in cervical dysplasia and cancers are far more important vaccine-related outcomes,” Dr. Perkins and her associates said. “Human papillomavirus vaccine protection must last many years to provide adequate cancer protection, therefore ongoing studies are paramount,” they noted.
The study used data from the Truven Health Analytics MarketScan Commercial Claims Database, covering enrollees and dependents from about half of provider-sponsored U.S. health insurance plans.
Read more at (Sex Transm Dis. 2017 Jun. doi: 10.1097/OLQ.0000000000000615).
Receiving two doses of human papillomavirus (HPV) vaccine at 5-month intervals or longer appears to provide similar protection against genital warts as three doses among girls initiating the series before age 15 years, reported Rebecca B. Perkins, MD, of Boston University, and her associates.
Of 387,906 adolescent females, 8% received 1 dose of HPV vaccine, 9% received 2 doses, 31% received 3 doses, and 52% remained unvaccinated. The mean age of the girls in the study was 15 years, and average length of follow-up was 6 years. The girls were aged 9-18 years on Jan.1, 2007, and the exposure period began at that time for unvaccinated girls or on the date of the last HPV vaccine injection for those receiving the vaccine. Among girls receiving more than 1 dose, 60% received their second dose within 3 months of their first dose (on time), and 47% received their third dose within 5 months of their second dose.
“Although reductions in genital warts are an important early marker of vaccine effectiveness, reductions in cervical dysplasia and cancers are far more important vaccine-related outcomes,” Dr. Perkins and her associates said. “Human papillomavirus vaccine protection must last many years to provide adequate cancer protection, therefore ongoing studies are paramount,” they noted.
The study used data from the Truven Health Analytics MarketScan Commercial Claims Database, covering enrollees and dependents from about half of provider-sponsored U.S. health insurance plans.
Read more at (Sex Transm Dis. 2017 Jun. doi: 10.1097/OLQ.0000000000000615).
FROM SEXUALLY TRANSMITTED DISEASES