A Paradigm Shift in Trauma ResuscitationEvaluation of Evolving Massive Transfusion Practices.


Importance  The evolution of damage control strategies has led to significant changes in the use of resuscitation after traumatic injury.

Objective  To evaluate changes in the administration of fluids and blood products, hypothesizing that a reduction in crystalloid volume and a reduced red blood cell (RBC) to fresh frozen plasma (FFP) ratio over the last 7 years would correlate with better resuscitation outcomes.

Design  Observational prospective cohort study.

Setting  Urban level I trauma center.

Participants  A total of 174 trauma patients receiving a massive transfusion (>10 units of RBCs in 24 hours) or requiring the activation of the institutional massive transfusion protocol from February 2005 to June 2011.

Exposure  Patients had to either receive a massive transfusion or require the activation of the institutional massive transfusion protocol.

Main Outcomes and Measures  In-hospital mortality.

Results  The mean (SD) Injury Severity Score was 28.4 (16.2), the mean (SD) base deficit was −9.8 (6.3), and median international normalized ratio was 1.3 (interquartile range, 1.2-1.6); the mortality rate was 40.8%. Patients received a median of 6.1 L of crystalloid, 13 units of RBCs, 10 units of FFP, and 1 unit of platelets over 24 hours, with a mean RBC:FFP ratio of 1.58:1. The mean 24-hour crystalloid infusion volume and number of the total blood product units given in the first 24 hours decreased significantly over the study period (P < .05). The RBC:FFP ratio decreased from a peak of 1.84:1 in 2007 to 1.55:1 in 2011 (P = .20). Injury severity and mortality remained stable over the study period. When adjusted for age and injury characteristics using Cox regression, each decrease of 0.1 achieved in the massive transfusion protocol’s RBC:FFP ratio was associated with a 5.6% reduction in mortality (P = .005).

Conclusions and Relevance  There has been a shift toward a reduced crystalloid volume and the recreation of whole blood from component products in resuscitation. These changes are associated with markedly improved outcomes and a new paradigm in the resuscitation of severely injured patients.

Source: JAMA


Telehealth Follow-up in Lieu of Postoperative Clinic Visit for Ambulatory Surgery.

Importance  Telehealth encounters can safely substitute for routine postoperative clinic visits in selected ambulatory surgical procedures.

Objective  To examine whether an allied health professional telephone visit could safely substitute for an in-person clinic visit.

Design  Prospective case series during a 10-month study period from October 2011 to October 2012 (excluding July and August 2012).

Setting  University-affiliated veterans hospital.

Patients  Ambulatory surgery patients who underwent elective open hernia repair or laparoscopic cholecystectomy during the 10-month study period.

Interventions  Patients were called 2 weeks after surgery by a physician assistant and assessed using a scripted template. Assessment variables included overall health, pain, fever, incision appearance, activity level, and any patient concerns. If the telephone assessment was consistent with absence of infection and return to baseline activities, the patient was discharged from follow-up. Patients who preferred a clinic visit were seen accordingly.

Main Outcomes and Measures  Percentage of patients who accepted telehealth follow-up and complications that presented in telehealth patients within 30 days of surgery.

Results  One hundred fifteen open herniorrhaphy and 26 laparoscopic cholecystectomy patients had attempted telehealth follow-up. Seventy-eight percent (110) of all patients were successfully contacted; of those, 70.8% (63) of hernia patients and 90.5% (19) of cholecystectomy patients accepted telehealth as the sole means of follow-up. Complications in the telehealth patients were zero for cholecystectomy and 4.8% (3) for herniorrhaphy. Nearly all patients expressed great satisfaction with the telephone follow-up method.

Conclusions  Telehealth can be safely used in selected ambulatory patients as a substitute for the standard postoperative clinic visit with a high degree of patient satisfaction. Time and expense for travel (7-866 miles) were reduced and the freed clinic time was used to schedule new patients.

Delivery of surgical care that is more efficient and cost-effective and has a high degree of patient satisfaction with excellent outcomes is a necessary evolution of the current surgical practice model. An in-person postoperative clinic evaluation is the “gold standard” throughout the United States. Some practices such as Kaiser Permanente use allied health care providers in lieu of surgeons to see the postoperative patients (N. Baril, MD, oral communication, December 12, 2012). The Veterans Health Care System provides care to eligible patients who come from sizeable catchment areas. The patients often must travel significant distances, which represent an investment on their part of time, missed work, and travel costs for a postoperative clinic visit that is typically quite brief. Therefore, as a quality initiative, we examined whether an allied health professional telephone visit could safely substitute for an in-person clinic visit.

For this pilot study, we defined a telehealth visit as a telephone call performed by a trained allied health care provider. This alternative has not been extensively studied, but a review of the literature demonstrates good patient satisfaction without compromise of overall patient care.1– 4 Several studies have shown that patients appreciate the ability to speak with their physicians or a physician’s surrogate by telephone and are highly satisfied with this mode of communication.1– 4 Advantages of telephone contact are the omission of clinic wait times and the elimination of the costs associated with traveling for an in-person clinic visit.2 Studies using telephone follow-up have been conducted in acute and chronic medical and surgical settings,4outpatient anorectal surgery,5 outpatient laparoscopic cholecystectomy,6 and pediatric adenotonsillectomy.7 These reports demonstrate that telephone encounters are safe for the patient and give the opportunity to provide advice and education and selectively identify individuals in need of actual in-person postoperative visits.2,4,8

Elective open hernia repairs and laparoscopic cholecystectomies are ambulatory procedures where potential complications are well characterized and infrequent.9– 10 The majority of postoperative clinic visits are often perfunctory with patients not having substantive issues that need acute medical attention. When there are complications, many of these patients present outside of the clinic visit with either a telephone call to the surgeon or to the emergency department. Therefore, these patients seemed to be the ideal cases that could be used for a pilot study before expanding to other ambulatory cases such as laparoscopic hernia repairs. Advantages to the patient would be convenience, no need to travel, and no loss of time. Advantages to the surgical service would be increased clinic access slots for new patients and decreased cost in the delivery of care.


Telehealth follow-up has been investigated and reviewed in various medical settings.1– 5,7– 8 Despite its demonstrated efficacy, there has not been widespread adoption in surgical practices. Our pilot study successfully demonstrates that patients who underwent elective open herniorrhaphy and laparoscopic cholecystectomy can be followed up safely by telehealth. Moreover, this approach has demonstrated acceptable complication assessment rates. Complications will occur after surgical procedures but the critical question to ask is whether there were any delays in diagnosis or worsened outcomes because of the lack of an in-person clinic visit. All but 1 of the hernia complications within 30 days were minor wound issues; the single serious complication of hematoma presented acutely and represented to the emergency department a second and third time even while being closely followed up in the clinic. No missed morbidity or mortalities were found on 30-day medical record review.

This pilot project was received very positively by our surgical staff and convincingly demonstrated to them that the vast majority of selected ambulatory patient follow-up could be done by telephone, with referral to the clinic based on the telephone evaluation. In the pilot, we learned that a process was necessary to facilitate completion of return-to-work or disability forms outside of a clinic visit. Our hospital is trying to expand the role of telehealth in the care of patients in our large catchment area. The director of the hospital telehealth program now recommends that a formal telehealth appointment be scheduled to set patients’ expectations. The 110 clinic slots that were opened up by use of this program were able to be used for new patients and helped improve clinic access and wait-time issues. We cannot provide any hospital cost data but a 10-minute physician assistant telephone call compared with a 5- to 10-minute surgeon visit in the clinic would most likely show a cost savings. More important is the savings of the patient’s time and resources to drive to the hospital for a brief and often cursory visit. In the cohort that accepted the telehealth visit, 51% had a round-trip driving distance of greater than 100 miles and 71% had a greater than 1 hour total commute.

Greater than 70% of patients contacted via telehealth willingly accepted this mode of communication for their postoperative care and no complaints were received. The observed low complication rate, none of which were directly tied to the lack of a postoperative clinic visit, helps demonstrate that patient care and outcomes were not compromised. It is our belief that this is applicable to non–veterans hospital practices. In general, people appreciate respecting their time, and elimination of a low-impact clinic visit while still maintaining patient contact through a telephone call should result in overall high patient satisfaction.

A potential weakness is the inference of cost savings to the system because a formal cost analysis was not performed. Since this was a pilot program, we can only infer conclusions about the true impact on health care costs. Overall, patients expressed satisfaction for our telehealth services, saving them from driving long distances and clinic wait times.

In conclusion, this pilot study demonstrated that a scripted telehealth visit by an allied health professional can be safely and effectively used for the postoperative care of open herniorrhaphy and laparoscopic cholecystectomy patients. There were no complications that resulted from the substitution of telehealth for a “gold standard” clinic visit. Expansion of telehealth follow-up to other selected procedures with low morbidities will be expanded within our service. The net results of increased clinic slots for new patients; patient satisfaction with avoiding travel; hospital cost savings by not using clinic space, resources, and staffing; and cost shifting the follow-up care from a physician to an allied health professional should all positively impact the cost of care for both the patient and the hospital. Evolution of care needs to continue with the aim of providing outstanding outcomes, at the lowest cost, and with a high degree of patient satisfaction. This program appears to satisfy all of these goals and is a direction that should be considered by other high-volume ambulatory practices, with care taken to select the correct mix of procedures.


Source: JAMA

Surgery Without Scars.

Report of Transluminal Cholecystectomy in a Human Being



Hypothesis  Natural orifice transluminal endoscopic surgery (NOTES) provides the potential for performance of incisionless operations. This would break the physical barrier between bodily trauma and surgery, representing an epical revolution in surgery. Our group at IRCAD-EITS (Institut de Recherche contre les Cancers de l’Appareil Digestif [Institute of Digestive Cancer Research]–European Institute of TeleSurgery) has been actively involved in the development of NOTES since 2004 with a dedicated project created to develop feasibility and survival studies and new endoscopic technology.

Design  NOTES cholecystectomy in a woman via a transvaginal approach.

Setting  University hospital.

Patient  The patient was a 30-year-old woman with symptomatic cholelithiasis.

Intervention  The procedure was carried out by a multidisciplinary team using a standard double-channel flexible videogastroscope and standard endoscopic instruments. The placement of a 2-mm needle port, mandatory to insufflate carbon dioxide and to monitor the pneumoperitoneum, was helpful for further retraction of the gallbladder. At no stage of the procedure was there need for laparoscopic assistance. All of the principles of cholecystectomy were strictly adhered to.

Results  The postoperative course was uneventful. The patient had no postoperative pain and no scars, and was discharged on the second postoperative day.

Conclusions  Transluminal surgery is feasible and safe. NOTES, a radical shift in the practice and philosophy of interventional treatment, is becoming established and is enormously advantageous to the patient. With its invisible mending and tremendous potential, NOTES might be the next surgical evolution.

The abolishment of pain in surgery is a chimera. It is absurd to go on seeking it. . . . Knife and pain are two words in surgery that must forever be associated in the consciousness of the patient.—Dr Alfred Velpeau, French surgeon (1839)

Change is part of surgery but it is never easy to accept. At the dawn of surgery, excellence was associated with big incisions: “Big scar, big surgeon.” Surgery with no scars was an impossible reverie. Now natural orifice transluminal endoscopic surgery (NOTES) is being performed, and the philosophy of surgery will be dramatically changed. Transluminal surgery has the potential to break the physical barrier between bodily trauma and surgery, representing an epical evolution in surgery.

Laparoscopic gallbladder resection changed the focus of surgery and the mindset of nearly all surgeons. Cholecystectomy seems to be the logical next step in developing the clinical application of NOTES.

In 1882, Langenbuch, as cited by van Gulik,1 successfully removed the gallbladder in a 43-year-old man who had cholelithiasis. His initial report was ignored. Nevertheless, Langenbuch’s open cholecystectomy remained the standard criterion for the treatment of symptomatic cholelithiasis for more than a century. In 1985, Muhe, as cited by Reynolds,2 performed the first laparoscopic cholecystectomy using a modified laparoscope, called the galloscope. In 1986, he presented his technique at the German Surgical Society Congress but was strongly criticized. In 1987, Mouret3performed the first laparoscopic cholecystectomy with an approach that would become the standard technique within 2 years, that is, use of 1 optical trocar and 2 other trocars. The world of general surgery was soon divided into a small group of enthusiastic surgeons convinced of the superiority of laparoscopic over conventional cholecystectomy and a second, large group of surgeons with varying opinions ranging from curiosity to frank condemnation of laparoscopic cholecystectomy.

The controversy was intense but short. In 1992, the National Institutes of Health Consensus Development Conference4 statement on gallstones and laparoscopic cholecystectomy concluded that, compared with open cholecystectomy, laparoscopic cholecystectomy was safe and effective in most patients and should be the treatment of choice. Even if surgeons were reluctant to acknowledge this shift in treatment, patients applauded the new minimally invasive surgery. Whenever it was possible, patients would ask for a surgical procedure that left no outer scarring and resulted in no postoperative pain. Patients, both male and female, independent of age and body shape, dislike scars, not only for cosmetic reasons but because scars indicate they have undergone treatment because of illness. This resulted in NOTES, with its general goal of minimizing the trauma of any interventional process by eliminating the incision through the abdominal wall and using natural orifices. To our knowledge, this is the first report of the use of NOTES to treat cholecystectomy in a human being via transvaginal access, performed at University Hospital in Strasbourg, France.


With the successful performance of the first transluminal cholecystectomy, we witnessed the introduction of NOTES into clinical practice with mixed feelings of excitement and caution. Even if the advantages of NOTES in this first clinical case are apparent, transvaginal cholecystectomy is time consuming and difficult. Will NOTES generate a major paradigm shift in surgical care? We know that laparoscopic surgery is just the beginning of the minimally invasive evolution of surgery. We have come to an even more critical juncture in the history of surgery. With its invisible mending and tremendous potential for improving patient care and well-being, NOTES might represent the next greatest surgical evolution.







Prevalence of Polypharmacy Exposure Among Hospitalized Children in the United States.


Objective  To assess the prevalence and patterns of exposure to drugs and therapeutic agents among hospitalized pediatric patients.

Design  Retrospective cohort study.

Setting  A total of 411 general hospitals and 52 children’s hospitals throughout the United States.

Patients  A total of 587 427 patients younger than 18 years, excluding healthy newborns, hospitalized in 2006, representing one-fifth of all pediatric admissions in the United States.

Main Outcome Measures  Daily and cumulative exposure to drugs and therapeutic agents.

Results  The most common exposures varied by patient age and by hospital type, with acetaminophen, albuterol, various antibiotics, fentanyl, heparin, ibuprofen, morphine, ondansetron, propofol, and ranitidine being among the most prevalent exposures. A considerable fraction of patients were exposed to numerous medications: in children’s hospitals, on the first day of hospitalization, patients younger than 1 year at the 90th percentile of daily exposure to distinct medications received 11 drugs, and patients 1 year or older received 13 drugs; in general hospitals, 8 and 12 drugs, respectively. By hospital day 7, in children’s hospitals, patients younger than 1 year at the 90th percentile of cumulative exposure to distinct distinct medications had received 29 drugs, and patients 1 year or older had received 35; in general hospitals, 22 and 28 drugs, respectively. Patients with less common conditions were more likely to be exposed to more drugs (P = .001).

Conclusion  A large fraction of hospitalized pediatric patients are exposed to substantial polypharmacy, especially patients with rare conditions.

In the United States, for persons young and old, exposure to medications is essentially universal.1Over the past decade, the relatively neglected area of pediatric drug effectiveness and safety has received increasing attention. The 2002 Best Pharmaceuticals for Children Act (BPCA),2 building on the 1997 US Food and Drug Administration Modernization Act,3– 4 set forth the goal of reducing pharmaceutical errors in the dispensing of drugs to hospitalized children. In the hospital setting, the efficacy and safety of many pediatric medications have not been well established5; much of the use of medications is for off-label indications6; and medication errors occur.5,7– 10 Both the BPCA and the complementary Pediatric Research Equity Act of 200311 have underscored the need for pediatric studies regarding both on- and off-label drug treatments12– 14 and for improvements in pediatric drug labeling.15– 16

To advance this agenda, we need to refine our knowledge of the overall patterns of pediatric inpatient drug and therapeutic agent use, including what drugs and therapeutic agents are used most commonly, the number of different drugs and therapeutic agents that hospitalized children receive, and potential differences in drug and therapeutic agent exposures across different types of hospitals. This knowledge, especially if based on population-level data, would enhance efforts to prioritize and design research studies regarding the effectiveness and safety of pediatric inpatient medications.17– 19

To address these objectives, we combined hospital medication use data from 2 large databases, the first of which comprises data exclusively from children’s hospitals while the second data set comprises data from mostly general hospitals; together these data sets represent approximately 19.9% of all pediatric inpatient hospitalizations in the United States. In this report, we examine drug and therapeutic agent use patterns among hospitalized pediatric patients (excluding healthy newborns) evident in the combined data, focusing on exposure to polypharmacy, which has been shown to be associated with an increased risk of adverse drug reactions in adult patients in intensive care units and other settings.20– 21

Source: JAMA


The Efficacy of Duct Tape vs Cryotherapy in the Treatment of Verruca Vulgaris (the Common Wart)


Objective  To determine if application of duct tape is as effective as cryotherapy in the treatment of common warts.

Design  A prospective, randomized controlled trial with 2 treatment arms for warts in children.

Setting  The general pediatric and adolescent clinics at a military medical center.

Patients  A total of 61 patients (age range, 3-22 years) were enrolled in the study from October 31, 2000, to July 25, 2001; 51 patients completed the study and were available for analysis.

Intervention  Patients were randomized using computer-generated codes to receive either cryotherapy (liquid nitrogen applied to each wart for 10 seconds every 2-3 weeks) for a maximum of 6 treatments or duct tape occlusion (applied directly to the wart) for a maximum of 2 months. Patients had their warts measured at baseline and with return visits.

Main Outcome Measure  Complete resolution of the wart being studied.

Results  Of the 51 patients completing the study, 26 (51%) were treated with duct tape, and 25 (49%) were treated with cryotherapy. Twenty-two patients (85%) in the duct tape arm vs 15 patients (60%) enrolled in the cryotherapy arm had complete resolution of their warts (P = .05 by χ2analysis). The majority of warts that responded to either therapy did so within the first month of treatment.

Conclusion  Duct tape occlusion therapy was significantly more effective than cryotherapy for treatment of the common wart.


In our study we found that the simple application of duct tape was more effective than cryotherapy in the treatment of the common wart. Cutaneous warts are a common diagnosis in the pediatric population, and many therapies exist for the treatment of these warts. Anecdotal reports have suggested the effectiveness of tape occlusion therapy. However, this is the first randomized, prospective study on the efficacy of tape occlusion therapy for warts. We also found that the warts that ultimately responded to tape therapy typically showed at least partial resolution after 2 to 3 weeks of treatment. Warts that were unchanged in appearance by the 3-week mark were unlikely to respond.

Several potential benefits exist for using duct tape over cryotherapy. Duct tape is more practical for parents and patients to use, especially when compared with the multiple clinic visits required for freezing of a wart. In today’s busy society, it can be difficult for parents to keep follow-up appointments every 2 weeks for cryotherapy of their children’s warts. In our study, the lower success rate of the cryotherapy arm is likely partially attributable to longer-than-optimal intervals between treatments in some patients. There was better compliance with the prescribed treatment regimen within the duct tape group, primarily due to the ease of administration. Another benefit of tape occlusion therapy is that it is much less costly than cryotherapy. The treatment can be undertaken in the home using inexpensive duct tape. Finally, tape occlusion therapy appears to be less threatening to a young child than freezing. The use of duct tape for the treatment of warts was generally well received by our patients.

Although both cryotherapy and tape occlusion therapy are well-tolerated treatments, the adverse-effect profile for tape occlusion therapy appears to be better. A variety of adverse effects with cryotherapy of warts have been previously reported, including pain during the procedure, erythema, hemorrhagic blister formation, dyspigmentation, recurrence of the wart, infection, and nail dystrophy when treating periungual warts.6 Although most patients tolerate the cryotherapy well, children 6 years and younger will typically remember previous applications as painful.12 In our study, all patients in the cryotherapy arm experienced pain, and 1 young child actually vomited in fear of pain before each application. The only adverse effect observed in the duct tape group during our study was a minimal amount of local irritation and erythema. Practical considerations limiting the use of duct tape therapy include difficulty for some patients in keeping the tape on, potential for exacerbation of underlying skin conditions such as eczema, and the cosmetic impracticality of using duct tape on the face.

Our study had several limitations. Because some parents were reluctant to make a return clinic visit if the wart had resolved, we did not have follow-up measurements of many of the warts in the clinic and had to rely on parental report of resolution over the telephone. This was more frequent in the duct tape arm because therapy in that arm took place in the home. To minimize this problem, we requested that parents closely examine the child for any residual wart. There was also difficulty in obtaining timely follow-up for many patients, which made our secondary end point of time to resolution more imprecise.

Our study indicates that duct tape is an effective treatment for warts that can be used as an alternative treatment to cryotherapy. Location of the wart might be related to efficacy of therapy. Our treatment arms were comparable in baseline location of the warts, but the relatively small number of patients in each treatment arm prevented us from determining whether wart locations made a difference in response to the occlusion therapy. We observed that some patients treated with duct tape had resolution of other untreated warts following elimination of the treated wart. We hypothesize this to be secondary to stimulation of the host’s immune system. Although our study was not designed to investigate the efficacy of treating one wart in the resolution of multiple warts, this would be an area for further investigation.

In conclusion, although many therapies exist for the eradication of warts, the use of duct tape appears promising as a safe and nonthreatening treatment modality for children. In our study, duct tape occlusion therapy was shown to be more effective than cryotherapy in the treatment of verruca vulgaris, and it caused few adverse effects.

Source: JAMA

Maternal Prenatal Smoking and Hearing Loss Among Adolescents.


Importance  Although smoking and secondhand smoke exposure are associated with sensorineural hearing loss (SNHL) in children and adults, the possible association between prenatal smoke exposure and hearing loss has not been investigated despite the fact that more than 12% of US children experience such prenatal exposure each year.

Objective  To investigate whether exposure to prenatal tobacco smoke is independently associated with SNHL in adolescents.

Design  Cross-sectional data were examined for 964 adolescents aged 12 to 15 years from the National Health and Nutrition Examination Survey 2005-2006.

Participants  Participants underwent standardized audiometric testing, and serum cotinine levels and self-reports were used to identify adolescents exposed to secondhand smoke or active smokers.

Main Outcomes and Measures  Prenatal exposure was defined as an affirmative parental response to, “Did [Sample Person’s Name] biological mother smoke at any time while she was pregnant with [him/her]?” Sensorineural hearing loss was defined as an average pure-tone hearing level more than 15 dB for 0.5, 1, and 2 kHz (low frequency) and 3, 4, 6, and 8 kHz (high frequency).

Results  Parental responses affirmed prenatal smoke exposure in 16.2% of 964 adolescents. Prenatal smoke exposure was associated with elevated pure-tone hearing thresholds at 2 and 6 kHz (P < .05), a higher rate of unilateral low-frequency SNHL (17.6% vs 7.1%; P < .05) in bivariate analyses, and a 2.6-fold increased odds of having unilateral low-frequency SNHL in multivariate analyses (95% CI, 1.1-6.4) after controlling for multiple hearing-related covariates.

Conclusions and Relevance  Prenatal smoke exposure is independently associated with higher pure-tone hearing thresholds and an almost 3-fold increase in the odds of unilateral low-frequency hearing loss among adolescents. These novel findings suggest that in utero exposure to tobacco smoke may be injurious to the auditory system.

Source: JAMA

Transoral Robotic Surgery for Oropharyngeal CancerLong-term Quality of Life and Functional Outcomes.


Importance  Because treatment for oropharyngeal squamous cell carcinoma (OPSCC), especially in patients of older age, is associated with decreased patient quality of life (QOL) after surgery, demonstration of a less QOL-impairing treatment technique would improve patient satisfaction substantially.

Objective  To determine swallowing, speech, and QOL outcomes following transoral robotic surgery (TORS) for OPSCC.

Design, Patients, and Setting  This prospective cohort study of 81 patients with previously untreated OPSCC was conducted at a tertiary care academic comprehensive cancer center.

Interventions  Primary surgical resection via TORS and neck dissection as indicated.

Main Outcomes and Measures  Patients were asked to complete the Head and Neck Cancer Inventory (HNCI) preoperatively and at 3 weeks as well as 3, 6, and 12 months postoperatively. Swallowing ability was assessed by independence from a gastrostomy tube (G-tube). Clinicopathologic and follow-up data were also collected.

Results  Mean follow-up time was 22.7 months. The HNCI response rates at 3 weeks and 3, 6, and 12 months were 79%, 60%, 63%, and 67% respectively. There were overall declines in speech, eating, aesthetic, social, and overall QOL domains in the early postoperative periods. However, at 1 year post TORS, scores for aesthetic, social, and overall QOL remained high. Radiation therapy was negatively correlated with multiple QOL domains (P < .05 for all comparisons), while age older than 55 years correlated with lower speech and aesthetic scores (P < .05 for both). Human papillomavirus status did not correlate with any QOL domain. G-tube rates at 6 and 12 months were 24% and 9%, respectively. Greater extent of TORS (>1 oropharyngeal site resected) and age older than 55 years predicted the need for a G-tube at any point after TORS (P < .05 for both).

Conclusions and Relevance  Patients with OPSCC treated with TORS maintain a high QOL at 1 year after surgery. Adjuvant treatment and older age tend to decrease QOL. Patients meeting these criteria should be counseled appropriately.

Source: JAMA


Randomized Clinical Trial Evaluating Intravitreal Ranibizumab or Saline for Vitreous Hemorrhage From Proliferative Diabetic Retinopathy.

Importance  Vascular endothelial growth factor plays a role in proliferative diabetic retinopathy (PDR). Intravitreal injection of saline has been shown potentially to lead to improved visual acuity compared with observation alone in eyes with vitreous hemorrhage. Therefore, it is important to determine if intravitreal anti–vascular endothelial growth factor can reduce vitrectomy rates (and risks associated with vitrectomy) compared with saline for vitreous hemorrhage from PDR that precludes placement or confirmation of complete panretinal photocoagulation.

Objective  To evaluate intravitreal ranibizumab compared with intravitreal saline injections on vitrectomy rates for vitreous hemorrhage from PDR.

Design  Phase 3, double-masked, randomized, multicenter clinical trial. Data reported were collected from June 2010 to March 2012 and include 16 weeks of follow-up.

Setting  Community-based and academic-based ophthalmology practices specializing in retinal diseases.

Participants  Two hundred sixty-one eyes of 261 study participants, who were at least 18 years of age with type 1 or type 2 diabetes mellitus. Study eyes had vitreous hemorrhage from PDR precluding panretinal photocoagulation completion.

Intervention  Eyes were randomly assigned to 0.5-mg intravitreal ranibizumab (n = 125) or intravitreal saline (n = 136) at baseline and 4 and 8 weeks.

Main Outcome Measure  Cumulative probability of vitrectomy within 16 weeks.

Results  Cumulative probability of vitrectomy by 16 weeks was 12% with ranibizumab vs 17% with saline (difference, 4%; 95% CI, −4% to 13%) and of complete panretinal photocoagulation without vitrectomy by 16 weeks was 44% and 31%, respectively (P = .05). The mean (SD) visual acuity improvement from baseline to 12 weeks was 22 (23) letters and 16 (31) letters, respectively (P = .04). Recurrent vitreous hemorrhage occurred within 16 weeks in 6% and 17%, respectively (P = .01). One eye developed endophthalmitis after saline injection.

Conclusions and Relevance  Overall, the 16-week vitrectomy rates were lower than expected in both groups. This study suggests little likelihood of a clinically important difference between ranibizumab and saline on the rate of vitrectomy by 16 weeks in eyes with vitreous hemorrhage from PDR. Short-term secondary outcomes including visual acuity improvement, increased panretinal photocoagulation completion rates, and reduced recurrent vitreous hemorrhage rates suggest biologic activity of ranibizumab. Long-term benefits remain unknown. Whether vitrectomy rates after saline or ranibizumab injection are different than observation alone cannot be determined from this study.


Source: JAMA




A 55-year-old woman presented with a 2-week history of low-grade fever and holocephalic headache, which mostly resolved but were followed by a 2-week history of increasing dizziness, imbalance, and falls as well as gradual subtle mental confusion. Her medical history was significant for living related-donor renal transplantation 15 years earlier after end-stage hypertensive nephropathy.

neuro caseOther medical history included hypertension, hyperthyroidism, osteoporosis, depression, and anxiety. Social history revealed no unusual travel or animal exposures and no history of tobacco, alcohol, or recreational drug use. Medications included cyclosporine, mycophenolate mofetil, prednisone, methimazole, aripiprazole, clonazepam, bupropion hydrochloride, and zolpidem tartrate. Examination revealed abnormal mental status, with reasonably good attention but some slowness, and decreased short-term and long-term memory. Findings on cranial nerve, motor, sensory, and reflex examinations were significant only for mild resting tremor of all extremities, minimal right arm weakness, and diffuse hyperreflexia. Magnetic resonance imaging showed multiple lesions on T2-weighted fluid attenuated inversion recovery (FLAIR) imaging involving white and gray matter (Figure 1). T1-weighted images after delivery of contrast showed multiple enhancing lesions, including 2 dominant enhancing masses in the right cerebellar hemisphere and in the corpus callosum (Figure 2). Lumbar puncture revealed opening pressure of 25 cm H2O, a white blood cell count of 10/μL, a red blood cell count of 4/μL, a protein concentration of 160 mg/dL, a glucose level of 55 mg/dL (with a blood glucose level of 102 mg/dL; to convert to millimoles per liter, multiply by 0.0555), and negative cultures. The patient became increasingly lethargic and dysphagic, without systemic signs of fever or infection. Repeated computed tomographic imaging suggested increasing edema around the dominant lesions.

Posttransplant Lymphoproliferative Disorder.



The history is of subacute symptoms mostly referable to the cerebellum but also consistent with a more central cerebral mass, as seen in the corpus callosum. Given the patient’s immunosuppression and the pronounced contrast enhancement, there was initial concern for an infectious mass or metastatic neoplasm. However, after lumbar puncture revealed only mild pleiocytosis and an elevated protein concentration as well as a normal glucose level and negative cultures, bacterial, fungal, and atypical bacterial causes seemed much less likely. There was no evidence for a primary malignant neoplasm, and the appearance of the lesions was not typical for metastatic disease. The involvement of gray matter in addition to white matter and the intense contrast enhancement made progressive multifocal leukoencephalopathy much less likely. Thus, the differential diagnosis was appropriately narrowed to posttransplant lymphoproliferative disorder vs central nervous system lymphoma. Further laboratory tests revealed active cytomegalovirus in the blood and high levels of Epstein-Barr virus genome in the cerebrospinal fluid. Bone marrow biopsy was uninformative and was negative for Epstein-Barr virus RNA. Because of her cognitive deterioration, a brain biopsy was performed. It revealed lymphohistiocytic infiltration with granuloma formation. However, in situ hybridization showed extensive presence of Epstein-Barr virus messenger RNA. All fungal and mycobacterial stains were negative. Immunophenotyping revealed a predominant T-cell population, with a subpopulation of B cells also present. There was no clear evidence for a clonal population indicative of lymphoma. A diagnosis of posttransplant lymphoproliferative disorder was made. This condition represents a polyclonal proliferative disorder related to Epstein-Barr virus infection of B cells. Typically, it occurs earlier in the course of immunosuppression but relates to the degree of immunosuppression and is typically reversible, although in some cases there may be subsequent development of frank lymphoma. Given her need for immunosuppression to retain her kidney transplant, she was given steroids and then high-dose methotrexate and rituximab. While she had some complications (including infections), she gradually improved, with mental status and gait returning to near baseline.

Source: JAMA



Gait Speed and Survival in Older Adults.

Context  Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates.

Objective  To evaluate the relationship between gait speed and survival.

Design, Setting, and Participants  Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34 485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6%, women; and 79.8%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s.

Main Outcome Measures  Survival rates and life expectancy.

Results  There were 17 528 deaths; the overall 5-year survival rate was 84.8% (confidence interval [CI], 79.6%-88.8%) and 10-year survival rate was 59.7% (95% CI, 46.5%-70.6%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19% to 87% in men and from 35% to 91% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization.

Conclusion  In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

Remaining years of life vary widely in older adults, and physicians should consider life expectancy when assessing goals of care and treatment plans.1 However, life expectancy based on age and sex alone provides limited information because survival is also influenced by health and functional abilities.2 There are currently no well-established approaches to predicting life expectancy that incorporate health and function, although several models have been developed from individual data sources.3– 5 Gait speed, also often termed walking speed, has been shown to be associated with survival among older adults in individual epidemiological cohort studies6– 12 and has been shown to reflect health and functional status.13 Gait speed has been recommended as a potentially useful clinical indicator of well-being among the older adults.14 The purpose of this study is to evaluate the association of gait speed with survival in older adults and to determine the degree to which gait speed explains variability in survival after accounting for age and sex.


Gait speed, age, and sex may offer the clinician tools for assessing expected survival to contribute to tailoring goals of care in older adults. The accuracy of predictions based on these 3 factors appears to be approximately similar to more complex models involving multiple other health-related factors, or for age, sex, use of mobility aids, and functional status. Gait speed might help refine survival estimates in clinical practice or research because it is simple and informative.

Why would gait speed predict survival? Walking requires energy, movement control, and support and places demands on multiple organ systems, including the heart, lungs, circulatory, nervous, and musculoskeletal systems. Slowing gait may reflect both damaged systems and a high-energy cost of walking.13,39– 54 Gait speed could be considered a simple and accessible summary indicator of vitality because it integrates known and unrecognized disturbances in multiple organ systems, many of which affect survival. In addition, decreasing mobility may induce a vicious cycle of reduced physical activity and deconditioning that has a direct effect on health and survival.6

The association between gait speed and survival is known.6– 7,9– 12,55– 56 Prior analyses used single cohorts and presented results as relative rather than absolute risk, as done herein. Similarly, mortality prediction models have been developed.3– 5,57– 60 Some models use self-reported information but others also include physiological or performance data, for a total of 4 to more than 10 predictive factors. Only a few models assess overall predictive capacity using C statistics; the reported values are in the range found in the present study (published area under the curve range, 0.66-0.8261 vs this study, 0.717 and 0.737).

The strengths of this study are the very large sample of individual participant data from multiple diverse populations of community-dwelling elders who were followed up for many years and use of consistent measures of performance and outcome. We provide survival estimates for a broad range of gait speeds and calculate absolute rates and median years of survival. Compared with prior studies that were too small to assess potential effect modification by age, sex, race/ethnicity, and other subgroups, we were able to assess multiple subgroup effects with substantial power. This study has the limitations of observational research; it cannot establish causal relationships and is vulnerable to various forms of healthy volunteer bias. The participating study cohorts, while large and diverse, do not represent the universe of possible data. Our survival estimates should be validated in additional data sets. Only 1 of the 9 studies was based in clinical practice,21 and advanced dementia is rare in populations who are competent to consent for research. However, median years of survival in this study resemble estimates for US adults across the sex and age range assessed.62 We were unable to assess the association of physical activity with survival in pooled analyses because measures of activity were highly variable across studies. Also, participants in these studies had no prior knowledge about the meaning of walking speed. In clinical use, participants might walk differently if they are aware of the implications of the results. Although this study provides information on survival, further work is needed to examine associations of other important pooled outcomes such as disability and health care use and to examine effects in populations more completely based in clinical practice.

Because gait speed can be assessed by nonprofessional staff using a 4-m walkway and a stopwatch,21 it is relatively simple to measure compared with many medical assessments. Nevertheless, methodological issues such as distance and verbal instructions remain.63– 64 Self-report is an alternative to gait speed for reflecting function. However, significant challenges remain in the use of self-report as well, such as choice of items and reliability, some of which can be addressed by emerging techniques such as computer adaptive testing based on item-response theory.65 The results found herein suggest that gait speed appears to be especially informative in older persons who report either no functional limitations or only difficulty with instrumental ADLs and may be less helpful for older adults who already report dependence in basic ADLs. The research studies analyzed herein used trained staff to measure gait speed. Staff in clinical settings would need initial training and may produce more variable results. Long-distance walks have become accepted in some medical fields and may contribute information beyond short walks.66– 68 However, the longer distance and time to perform the test may limit feasibility in many clinical settings. Although the sample size of very slow walkers was small, our data suggest that there may be a subpopulation who walk very slowly but survive for long periods. It would be valuable to further characterize this subgroup.

Although the gait speed–survival relationship seems continuous across the entire range, cut points may help interpretation. Several authors have proposed that gait speeds faster than 1.0 m/s suggest healthier aging while gait speeds slower than 0.6 m/s increase the likelihood of poor health and function.7,21 Others propose one cutoff around 0.8 m/s.13 In our data, predicted life expectancy at the median for age and sex occurs at about 0.8 m/s; faster gait speeds predict life expectancy beyond the median. Perhaps a gait speed faster than 1.0 m/s suggests better than average life expectancy and above 1.2 m/s suggests exceptional life expectancy, but additional research will be necessary to determine this relationship.

How might gait speed be used clinically? First, gait speed might help identify older adults with a high probability of living for 5 or 10 more years, who may be appropriate targets for preventive interventions that require years for benefit. Second, gait speed might be used to identify older adults with increased risk of early mortality, perhaps those with gait speeds slower than 0.6 m/s. In these patients, further examination is targeted at potentially modifiable risks to health and survival. A recommended evaluation and management of slow walking includes cardiopulmonary, neurological and musculoskeletal systems.6,18 Third, gait speed might promote communication. Primary clinicians might characterize an older adult as likely to be in poor health and function because the gait speed is 0.5 m/s. In research manuscripts, baseline gait speed might help to characterize the overall health of older research participants. Fourth, gait speed might be monitored over time, with a decline indicating a new health problem that requires evaluation. Fifth, gait speed might be used to stratify risks from surgery or chemotherapy. Finally, medical and behavioral interventions might be assessed for their effect on gait speed in clinical trials. Such true experiments could then evaluate causal pathways to determine whether interventions that improve gait speed lead to improvements in function, health, and longevity.

The data provided herein are intended to aid clinicians, investigators, and health system planners who seek simple indicators of health and survival in older adults. Gait speed has potential to be implemented in practice, using a stop watch and a 4-m course. From a standing start, individuals are instructed to walk at their usual pace, as if they were walking down the street, and given no further encouragement or instructions. The data in this article can be used to help interpret the results. Gait speed may be a simple and accessible indicator of the health of the older person.

Source: JAMA