Physiotherapy Equipment Market Is Expected To Grow At A Cagr Of 6.35% By 2020

Physiotherapy is a technique that uses various procedures and equipment to relieve physical ailments. It has evolved from a simple massage to a complex variety of treatments. It is an essential part of rehabilitation after surgeries, chemotherapy, and radiation procedures to promote mobility. Physiotherapy plays a significant role for physically challenged people and provides relief to the patients with injuries and chronic disorders such as stroke, arthritis, and cerebral palsy.

Browse the full report @:

How Big is the Global Physiotherapy Equipment Market?

The global physiotherapy equipment market to grow at a CAGR of 6.35% over the period 2014-2020.

The report covers the current scenario and the growth prospects of the global physiotherapy equipment market for the period of 2015-2020. To calculate the market size, the report considers revenue generated through sales of the following product categories:


Table of Contents

2 Research Methodology

3 Executive Summary

4 Premium Insights

5 Market Overview

6 Industry Insights

7 Physiotherapy Equipment Market,By Product

8 Physiotherapy Equipment Market, By Application

9 Physiotherapy Equipment Market, By End User

10 Geographic Analysis

11 Competitive Landscape

12 Company Profiles

12.1 Introduction

12.2 Djo Global/ Chattanooga

12.3 EMS Physio Ltd.

12.4 ENRAF-Nonius B.V.

12.5 BTL Industries Inc.

12.6 Isokinetics , Inc.

12.7 Patterson Companies Inc.

12.8 Morris Group Internationals

12.9 HMS Medical Systems

12.10 Dynatronics Corporation

12.11 Body Sport


Perioperative Physiotherapy in Total Knee Arthroplasty

Melvin G. Joice, BSE; Subhrojyoti Bhowmick, MD; Derek F. Amanatullah, MD, PhD

Posted May 22, 2017
DOI: 10.3928/01477447-20170518-03


Total knee arthroplasty has a high success rate. In the interest of enhancing patient outcomes, numerous perioperative interventions have been studied, including preoperative education, preoperative rehabilitation, postoperative inpatient rehabilitation, continuous passive motion, postoperative outpatient rehabilitation, unsupervised in-home exercises, telerehabilitation, and various combinations of these. This comprehensive review analyzes the existing body of evidence on these perioperative interventions and examines some burgeoning opportunities in rehabilitation after total knee arthroplasty in the interest of improving patient outcomes and ensuring sustainable health care utilization for the future of total knee arthroplasty. [Orthopedics. 201x; xx(x):xx–xx.]

Total knee arthroplasty (TKA) is the gold standard of treatment for patients with end-stage arthritis of the knee. As of 2010, more than 620,000 TKA procedures were performed annually in the United States.1 By 2030, this is predicted to reach 3.5 million annually.2 Even with these high volumes, the 2003 National Institutes of Health consensus statement on TKA concluded that “the use of rehabilitation services is perhaps the most under-studied aspect of the perioperative management of TKA patients . . . [and] there is no evidence supporting the generalized use of any specific pre-operative or post-operative rehabilitation intervention.”3 In response to this statement, investigators have reported on a plethora of rehabilitative techniques and regimens available for perioperative management of TKA patients. In the United States, rehabilitation after TKA refers to several different practice settings depending on the patient, the health care system, and treatment decisions made by both the health care team and the patient. “Rehabilitation” begins at or before entering the acute inpatient setting, where decisions are made concerning the most appropriate discharge location for the patient. Possible discharge locations for a patient after TKA are a skilled nursing facility, an inpatient rehabilitation facility, home with home health physical therapy, home with a prescribed home exercise program, or outpatient physical therapy.4 Müller et al5 observed that best practice in rehabilitation is largely based on clinical experience, local customs, anecdotal evidence, surgeon preferences, clinical pathways established for the acute-care phase of recovery, and health insurance funding schemes.

This review reports the numerous available rehabilitation options, highlights the regimens with the highest level of evidence-based consensus, and examines some burgeoning opportunities in rehabilitation that may be necessary to keep pace with the increasing demand for TKA.

Materials and Methods
Search and Selection

In May 2016, a thorough search was conducted of MEDLINE (from 1966), the Cochrane Library, and the Physiotherapy Evidence Database (PEDro). Included were studies published in English, concerning perioperative interventions for primary TKA, with well-established outcome measures, considered randomized controlled trials (RCTs), with a matched cohort, considered comparative retrospective case series, and considered applicable Cochrane reviews and meta-analyses. Excluded studies included those with data not reported, those with nonquantitative outcome measures, or those published prior to 1985. Search terms included total knee arthroplasty, physiotherapy, rehabilitation, management, preoperative, postoperative, continuous passive motion, telerehabilitation, in-home exercises, neuromuscular electric stimulation, diet, and Wii as isolated terms and in combination.

Data Analysis

For specific interventions that had sufficient data, a forest plot was constructed to analyze effectiveness. Only continuous passive motion (CPM) as an intervention had enough data in the existing literature to be analyzed. Any study since 1990 that had adequate reporting of data to analyze was included. Of the 28 studies found concerning CPM, 17 were included.6–22 Eleven studies were not included, mainly due to incomplete data reporting.23–34 Of the excluded studies, some did not report standard deviations, others did not use a standard protocol for the measurement of range of motion (ROM), and one was out-side the date range specified in the inclusion criteria.

To generate the forest plots, the standardized mean differences between treatment groups on each outcome were calculated at each time point for which data were available, as well as 95% confidence intervals for these effects. These effect size estimates were then pooled across the subset of studies making the same treatment comparisons at the same time points using standard random effects meta-analytic methods. All analyses and plotting were accomplished using the rmeta, meta, and es.compute libraries of the R statistical program (version 3.0.0; R Foundation) released in 2014.

Preoperative Interventions

Preoperative Patient Education. Pre-operative education refers to any educational intervention delivered before surgery that aims to improve the patients’ knowledge, perspectives, health behaviors, and/or health outcomes.35–37 Although the content of preoperative education varies, it often includes discussion of administrative procedures, the surgical procedure, postoperative care, potential stressful scenarios, potential complications, pain management, and movements to perform or avoid after surgery.38

Chen et al39 randomized patients (n=92) to receive either a pamphlet or educational videos and a skill-teaching session for rehabilitation or usual standard care. Patients receiving the additional materials reported lower pain scores up to 2 days postoperatively; after that, the only significant differences were in stair climbing time, eating, and the regularity of performing straight-leg raises. Crowe and Henderson40 provided patients (n=133) with a 50-minute video, an informational booklet, a tour of the postoperative hospital unit, and a demonstration of how to use the postoperative equipment. Although they found that length of stay (LOS) could be reduced by offering comprehensive individualized educational materials for patients, they did not find significant differences in joint flexion, the 30-minute walking test, or stair climbing.40 Encompassing 12 similar studies (n=1567), a systematic review conducted in 2015 analyzed the effect of preoperative education on anxiety, pain, LOS, patient satisfaction, postoperative complications, mobility, and expectations. Among these outcomes, preoperative education was only found to be effective in reducing preoperative patient anxiety.41

Current evidence seems to indicate that a focus on preoperative education has little clinical benefit. Although preoperative education should remain a part of the clinical pathway in TKA, no extra resources or time apart from the standard of care seems to be indicated currently.

Physiotherapy/Prehabilitation. Preoperative physiotherapy or “prehabilitation,” whether in a home setting or a clinical setting, is theorized to improve postoperative TKA outcomes by increasing knee ROM and strengthening the quadriceps muscles before surgery. A graphical representation of this theory, similar to one presented by Ditmyer et al,42 is shown in Figure 1.

Proposed prehabilitation model. It is postulated that rehabilitation before surgery results in better postoperative outcomes. Abbreviation: TKA, total knee arthroplasty.

Figure 1:
Proposed prehabilitation model. It is postulated that rehabilitation before surgery results in better postoperative outcomes. Abbreviation: TKA, total knee arthroplasty.

In 2007, Williamson et al43 (n=181) administered a 6-week course of preoperative physiotherapy that included “static quadriceps contractions, inner range quadriceps contractions, straight leg raises, sit-to-stands, stair climbing, calf stretches, theraband resisted knee extensions, wobble board balance training, knee flexion/extension sitting on gym ball, and free-standing peddle revolutions.” They found no significant differences in LOS, Oxford knee score, 50-minute walking test, visual analog scale score, or Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Mitchell et al44 conducted an RCT (n=160) comparing patients who received preoperative and postoperative physiotherapy with those who received only postoperative physiotherapy. Preoperative physiotherapy included pain relief, techniques to increase knee flexion and extension, gait reeducation, and functional adaptations.44 For all outcome measures, including WOMAC, stiffness, and Short Form-36 scores, the authors found no significant differences for patients receiving the extra preoperative physiotherapy.

Contrastingly, some studies have found significant short-term differences in post-operative outcomes when administering preoperative physiotherapy to TKA patients. In 2014, Matassi et al45 randomized patients (n=122) to either receive a preoperative 6-week home-based exercise program or continue normal activities until surgery. With a 79% compliance rate with the at-home regimen, the authors concluded that preoperative home-based exercise offered a boon in short-term knee ROM, but had no significant effect on knee ROM or Knee Society score 1 year after TKA.45

Despite the body of evidence mounting against both preoperative education and preoperative physiotherapy individually, it was hypothesized that combining these interventions might offer superior post-operative outcomes in TKA. Beaupre et al46 randomized patients (n=131) to either a combined education/exercise program that consisted of 3 sessions for 4 weeks preoperatively or a control group that received usual care. They found no significant differences in ROM, pain, function, or health-related quality of life up to 1 year after TKA.46

Overall, recent reviews and meta-analyses unanimously agree that patient outcomes are not significantly affected in the long-term by preoperative physiotherapy regimens.47–49 Wallis and Taylor49 hypothesized that preoperative physiotherapy shows little effect because “it is possible that marked reduction of pain that comes from replacing painful joint surfaces during surgery far outweighs modest contribution from pre-operative interventions.” An alternative hypothesis is that patients are so significantly deconditioned from the surgery that any benefits gained from preoperative rehabilitation are muted.50 The revised model for the effects of preoperative physiotherapy is shown in Figure 2. Currently, preoperative rehabilitation is rarely prescribed by surgeons because of the lack of long-term postoperative benefits.51

Figure 2:
Actual prehabilitation model. By current evidence, rehabilitation before surgery does not affect postoperative outcomes. Abbreviation: TKA, total knee arthroplasty.

Short-term Postoperative Interventions

Inpatient Rehabilitation. Inpatient rehabilitation refers to any intervention that follows immediately after TKA and prior to initial discharge. Although there is large consensus on the importance of a rehabilitation regimen immediately following TKA, little agreement exists on the exercises that comprise the regimen, the intensity of exercises, and the duration. Recent regimens reported in the literature vary in duration from 3 to 14 days and have employed interventions such as walking, stretching, gait retraining, CPM, aquatic therapy, quadriceps strengthening exercises, and stair climbing exercises. Contemporary inpatient regimens have shorter durations and more intense exercises and begin on the day of surgery or the first postoperative day.

Aggressive rehabilitation is believed to be important in preventing postoperative contracture of the soft tissue and in gaining better flexion postoperatively. Pua and Ong52 (n=1504) studied the significance of ambulation on the first postoperative day and found that it resulted in a significantly shorter LOS, lower hospitalization costs, and improved knee function. Zietek et al53 (n=66) increased the intensity of rehabilitation on the first postoperative day by adding an extra 15-minute walk with a walker 3 hours after an initial 15-minute walk. They found no detriment to the added intensity and suggested a further increase in intensity. However, when Lenssen et al54 (n=43) increased inpatient rehabilitation intensity to 2 physical therapy sessions a day in an RCT, they found no significant gain in ROM.

Isaac et al55 randomized patients (n=50) to investigate an accelerated rehabilitation protocol that included infiltration of bupivacaine and adrenaline into the divided tissue layers at the time of surgery, spinal anesthesia, mobilization on the day of surgery, an organized multidisciplinary approach anticipating issues that may delay discharge, and an expectation of an earlier discharge from the hospital. They showed a 6.9-day decrease in LOS, with comparable pain levels, Knee Society score, and Oxford knee score. Similarly, in a randomized clinical trial (n=185), a rapid recovery protocol after TKA was tested in a low-resource military hospital setting; the protocol included preoperative patient education, ambulation on the first postoperative day, and pain management with celecoxib and oxycodone.56 The protocol decreased LOS by 2.9 days and saved an average of $1511 in hospitalization costs without causing any adverse health outcomes.

Overall, inpatient rehabilitation in the immediate postoperative setting is the most important intervention in perioperative management of TKA. In recent years, the regimens have become shorter and more aggressive, including postoperative ambulation on the day of surgery or the first day following surgery. There is evidence to indicate that shorter courses of rehabilitation do not adversely affect patients and are beneficial in terms of LOS and hospitalization costs.

Continuous Passive Motion. The mechanism of CPM has been hypothesized to be twofold: facilitating the movement of synovial fluid to allow for better diffusion of nutrients into damaged cartilage with diffusion of other materials out, and preventing fibrous scar tissue formation in the joint, which tends to decrease ROM.

Studies on the use of CPM have had conflicting results. Early studies indicated that CPM had a short-term benefit after TKA by increasing knee ROM and improving wound healing.27 Other studies purported that CPM may be optimized if initiated immediately after TKA.11,15,23,31,57 However, more recent studies seem to refute these findings, claiming no benefit in CPM after TKA.6–8,18–20,28,29,32–34,58 In an attempt to make sense of the conflicting evidence, several systematic reviews have been conducted. However, these reviews have had conflicting conclusions as well. Older reviews seem to favor the use of CPM,59.60 while more recent reviews seem to show no benefit.61,62

Conflicting conclusions of the systematic reviews were a result of different inclusion and exclusion criteria. Reviews that included studies in which post-TKA patients who received CPM were compared with patients whose knees were immobilized found a benefit with CPM. Contrastingly, reviews that only included studies in which patients who received CPM were compared with patients who received conventional physiotherapy found no benefit with CPM. This difference in comparison explains why earlier reviews found CPM to be beneficial—they were conducted at a time when the standard of care for acute postoperative TKA was knee immobilization. More recent reviews compared CPM with the current standard of care, physiotherapy, and found no difference. Thus, critical scrutiny of the literature against the backdrop of normal clinical practice provides a unified conclusion supporting postoperative rehabilitation in TKA, in the form of conventional physiotherapy or CPM, because knee motion is more beneficial than knee immobilization. Further, this unified conclusion supports the idea that CPM offers little to no additional benefit to conventional postoperative physiotherapy.

To validate the unifying theory concerning discordant conclusions in CPM studies and meta-analyses, forest plots were generated that stratified the control group to either postoperative immobilization or physical therapy. In the CPM vs immobilization data analysis, ROM was analyzed at time points of 3 and 12 months (Figure 3). The pooled data showed no significant ROM improvement at either time point. In the CPM vs physical therapy data analysis, the time points included discharge, 3 months, 6 months, and 12 months (Figure 4). Regardless of time point, none of the changes in ROM represented a clinically significant difference with the use of CPM when compared with the use of physical therapy.

Continuous passive motion (CPM) vs immobilization (IM) at 3 months and 12 months. With just a few studies, conclusions are difficult to draw. However, a few studies found CPM, compared with IM, to be helpful in increasing range of motion. Abbreviation: CI, confidence interval.

Figure 3:
Continuous passive motion (CPM) vs immobilization (IM) at 3 months and 12 months. With just a few studies, conclusions are difficult to draw. However, a few studies found CPM, compared with IM, to be helpful in increasing range of motion. Abbreviation: CI, confidence interval.

Continuous passive motion (CPM) vs physical therapy (PT) at discharge, 3 months, 6 months, and 12 months. At all time points, CPM was not found to be helpful in increasing range of motion. Abbreviation: CI, confidence interval.

Figure 4:
Continuous passive motion (CPM) vs physical therapy (PT) at discharge, 3 months, 6 months, and 12 months. At all time points, CPM was not found to be helpful in increasing range of motion. Abbreviation: CI, confidence interval.

Comparing the 2 stratified analyses, the largest absolute mean difference was seen in CPM vs immobilization at 12 months. This offers some insight into why CPM was thought to be beneficial when compared with immobilization but not when compared with physical therapy. Overall, the authors’ analysis of current literature suggests that there is little benefit to any patient receiving CPM after primary TKA in the backdrop of the current standard of care that includes postoperative physical therapy, indicating that CPM is an unnecessary overuse of medical resources.

Long-term Postoperative Interventions

Outpatient Physical Therapy. Physical therapy that begins after hospital discharge has long been considered the standard of care in the rehabilitation after TKA, reliably facilitating ROM, strength, and quality of life improvements. Outpatient rehabilitation can range from 3 to 8 weeks and can include multiple sessions per week. Ebert et al63 (n=108) noted that active knee flexion at the beginning of outpatient visits correlates strongly with knee flexion at 7 weeks after TKA, underscoring the importance of rehabilitation even after hospital discharge. Similarly, Brennan et al64 (n=321) recently reported that an increase in the number of days between hospital discharge and outpatient physical therapy was a significant factor in the prediction of disability and pain scores at the completion of rehabilitation, with an increase in the number of days correlating with an increase in pain and disability. In a survey of physiotherapists concerning best practices for rehabilitation, participants agreed that “aggressive physiotherapy should be met within 8 weeks, as the knee can become stiff as a result of tissue scarring down from lack of mobility.”65

A key research issue, of recent importance due to the increased demands placed on rehabilitation services, has been the use of group physical therapy vs individual physical therapy. Naylor et al66 surveyed 93 TKA patients after their rehabilitation was complete and found no overall preference for either mode. The authors also confirmed the strengths of each mode: group-based therapy granted a psychosocial benefit, whereas the one-to-one therapy offered a more personalized approach. Aprile et al67 conducted a randomized, single-blind, crossover study (n=27) comparing individual and group rehabilitation. They found no significant differences in Short Form-36, WOMAC, and visual analog scale scores between patients at 1 month after TKA.67 Similarly, Ko et al68 conducted a randomized, superiority trial (n=249) comparing one-to-one therapy, group-based therapy, and a monitored home program. They found that “one-to-one therapy does not provide superior self-reported or performance-based outcomes compared with group-based therapy or a monitored home program, in the short term and the long term after total knee arthroplasty.”68 The outcome measures included the Oxford knee score, WOMAC score, and Short Form-12 score.

Outpatient physical therapy remains relevant in the clinical pathway following primary TKA; however, current trends indicate a shift toward patient-specific regimens. Because evidence suggests both group therapy and individual therapy are viable options, patients can be assigned according to their individual preferences concerning physical therapy.

Home Exercises and In-Home Telerehabilitation. Both home exercise regimens delivered via a physician handout containing diagrammed exercises and telerehabilitation involving physical therapists interacting via live, 2-way video feeds have recently garnered attention as resource-saving rehabilitation modalities.

According to Dr Froimson, President of the Cleveland Clinic Health System, “The goals of a home-based clinical care path . . . include patient and family engagement, shared decision-making, and flexibility regarding changes in plans to accommodate changing needs.”69 He continued, “Patients discharged home consume significantly fewer resources and cost the system about one-third as much as those sent to an inpatient postacute facility.” In a recent RCT (n=34), Buker et al70 compared supervised physiotherapy with home exercises. They found no differences in visual analog scale score, ROM, WOMAC score, and Short Form-36 score between the groups and noted that home exercises were approximately $209 less expensive. Similarly, Rajan et al71 randomized patients (n=120) to receive either usual-care physiotherapy or a well-structured home exercise regimen. At 1-year follow-up, only a clinically insignificant difference of 2.9° in ROM was seen. Kramer et al72 randomized patients similarly (n=160) and found no significant differences in Knee Society score, WOMAC score, Short Form-36 score, 6-minute walking test, 30-second stair climbing time, and knee flexion ROM at 3 months and 1 year after TKA. Han et al73 confirmed these findings in a multicenter, noninferiority RCT (n=490). They reported no significant differences in pain, knee function, ROM, or 50-foot walk times at 6 weeks postoperatively. Home-based care, as per current evidence, is a viable and more efficient alternative to outpatient rehabilitation.

Telerehabilitation is a newer medium for postoperative rehabilitation; advances in technology and Internet availability have made wider use of these technologies possible. Russell et al74 conducted an RCT (n=65) evaluating the equivalence of an Internet-based telerehabilitation program with conventional outpatient physical therapy. The authors noted comparable ROM, muscle strength, limb girth, pain, timed up-and-go, quality of life, gait, and WOMAC scores. They also noted that the telerehabilitation intervention was well received by participants, who reported a high level of satisfaction with this novel technology.74 Similarly, a higher-powered RCT (n=205) that compared face-to-face home rehabilitation with telerehabilitation found the latter to be noninferior in terms of WOMAC score, knee injury and osteoarthritis outcome score, knee function, knee strength, and ROM.75 Examining cost concerns, Tousignant et al76 used an RCT (n=197) to compare telerehabilitation with home-visit rehabilitation. The authors found telerehabilitation to be less expensive via a total cost analysis—a differential of -$263 (95% confidence interval, -$382 to -$143) in Canadian dollars.76 However, in lieu of a net analysis, telerehabilitation was only significantly less expensive when the patient lived more than 30 km from the health care center. Telerehabilitation offers yet another way for health care professionals to account for patient-specific factors in prescribing postoperative physical therapy. For patients with the technological accessibility and savvy, a telerehabilitation regimen may be indicated.

Adjunctive Interventions

Neuromuscular Electric Stimulation. In an attempt to improve TKA outcomes, an array of adjunctive interventions is under investigation. Neuromuscular electric stimulation (NEMS) involves electrical stimulation of lower limb muscles using a transcutaneous electrical nerve stimulation system. Neuromuscular electric stimulation is hypothesized to improve muscle strength of the quadriceps and to train patients without sufficient volitional quadriceps activation by engaging neuro-physiological mechanisms after TKA.77

Levine et al,78 in an RCT (n=70), showed that NMES combined with unsupervised at-home exercises was noninferior to traditional supervised physiotherapy at 6 months postoperatively regarding flexion, extension, Knee Society score, WOMAC score, and timed up-and-go. In a small RCT (n=30), Avramidis et al79 applied NMES to the vastus medialis for 6 weeks postoperatively as an adjunct to conventional physical therapy. The authors found a significant increase in walking speed at 3 months, but the Hospital for Special Surgery knee score was unchanged.79 Similarly, Demircioglu et al80 (n=60) applied an adjunctive NMES protocol—5 days a week for 4 to 6 weeks—to a standard exercise protocol in an RCT. They found that NMES improved ROM and timed up-and-go at 1 month but not at 3 months postoperatively. They also measured better WOMAC scores at both 1 and 3 months. The authors concluded that NMES therapy added to a standard exercise protocol offers superior outcomes.80 Although few studies have examined the long-term effects of NMES, in a small RCT (n=35), Stevens-Lapsley et al81 noted that improvements in quadriceps strength, hamstring strength, stair climbing time, timed up-and-go, and 6-minute walking test persisted until 1 year after TKA. In a high-powered RCT (n=200), Petterson et al82 showed that strength, activation, and function were similar between the exercise and exercise–NMES groups at 3 and 12 months. However, both groups were stronger and exhibited better function than the standard-of-care group at both time points.

Overall, NMES is a relatively new modality in the postoperative course of primary TKA. Preliminary evidence suggests a slight improvement in clinical outcomes with the use of NMES.

Wii-Based Home Rehabilitation. Balance training has been included in rehabilitation after TKA.83,84 Given the recent prevalence of Wii (Nintendo, Kyoto, Japan) console systems in homes and the inclusion of Wii Fit, the concept of Wii-based home rehabilitation via balance training has emerged as an adjunct to traditional physiotherapy. Wii Fit games encourage lower extremity movement, challenge balance, and require players to remain in a standing position during play—activities that have the potential to address rehabilitation goals involving recovery of lower extremity function.85 McPhail et al86 (n=18) conducted a preliminary trial in patients recovering from lower limb fractures. The Wii Fit regimen failed to show clinically meaningful differences in a range of measurements, including gait parameters, lower extremity functional scale, and step test.86 Similarly, in an RCT (n=50), Fung et al85 administered 15-minute sessions of Wii Fit after traditional physical therapy sessions. They found no significant differences between the groups regarding pain, knee flexion, knee extension, walking speed, timed standing tasks, lower extremity functional scale, activity-specific balance confidence scale, and patient satisfaction with therapy services.85

Clinical Relevance

In the lengthy clinical pathway from scheduling a patient for TKA to the patient’s resuming normal activity, many options—old and new—exist in the interest of maximizing patient outcome. Overall, evidence seems to suggest that preoperative rehabilitation and education are unsuccessful at enhancing outcomes. Inpatient rehabilitation remains a mainstay before releasing a patient and is effective. Continuous passive motion has been heavily investigated without much consensus, but the current authors’ analysis along with recent evidence supports the conclusion that CPM offers little benefit to primary TKA patients in lieu of standard-of-care physical therapy. Outpatient rehabilitation is incredibly popular. However, given its cost, inconvenience, and increased load on limited health care resources, outpatient rehabilitation is being slowly replaced by unsupervised home exercises and telerehabilitation without any adverse effects. Adjunctive therapies such as NMES have begun to emerge, but their long-term advantage needs to be substantiated. New opportunities such as mobile application–based physical therapy hold promise in enhancing patient satisfaction and reducing health care resource utilization by granting increased autonomy, digitizing patient management, identifying outliers for more intensive therapy, and potentially enhancing outcomes. These new opportunities require further investigation and hold promise for a health care utilization scheme that can adequately manage the increasing demand for TKA services.


Steiner C, Andrews R, Barrett M, Weiss A. HCUP projections: mobility/orthopedic procedures 2003 to 2012. Accessed June 17, 2015.
Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007; 89(4):780–785.
NIH Consensus Statement on total knee replacement. NIH Consens State Sci Statements. 2003; 20(1):1–34.
Lingard EA, Berven S, Katz JNKinemax Outcomes Group. Management and care of patients undergoing total knee arthroplasty: variations across different health care settings. Arthritis Care Res. 2000; 13(3):129–136. doi:10.1002/1529-0131(200006)13:33.0.CO;2-6 [CrossRef]
Müller E, Mittag O, Gülich M, Uhlmann A, Jäckel WH. Systematic literature analysis on therapies applied in rehabilitation of hip and knee arthroplasty: methods, results and challenges [in German]. Rehabilitation (Stuttg). 2009; 48(2):62–72. doi:10.1055/s-0029-1202295 [CrossRef]
Bruun-Olsen V, Heiberg KE, Mengshoel AM. Continuous passive motion as an adjunct to active exercises in early rehabilitation following total knee arthroplasty: a randomized controlled trial. Disabil Rehabil. 2009; 31(4):277–283. doi:10.1080/09638280801931204 [CrossRef]
Denis M, Moffet H, Caron F, Ouellet D, Paquet J, Nolet L. Effectiveness of continuous passive motion and conventional physical therapy after total knee arthroplasty: a randomized clinical trial. Phys Ther. 2006; 86(2):174–185.
Chiarello CM, Gundersen L, O’Halloran T. The effect of continuous passive motion duration and increment on range of motion in total knee arthroplasty patients. J Orthop Sports Phys Ther. 1997; 25(2):119–127. doi:10.2519/jospt.1997.25.2.119 [CrossRef]
Lau SK, Chiu KY. Use of continuous passive motion after total knee arthroplasty. J Arthroplasty. 2001; 16(3):336–339. doi:10.1054/arth.2001.21453 [CrossRef]
MacDonald SJ, Bourne RB, Rorabeck CH, McCalden RW, Kramer J, Vaz M. Prospective randomized clinical trial of continuous passive motion after total knee arthroplasty. Clin Orthop Relat Res. 2000; 380:30–35. doi:10.1097/00003086-200011000-00005 [CrossRef]
Montgomery F, Eliasson M. Continuous passive motion compared to active physical therapy after knee arthroplasty: similar hospitalization times in a randomized study of 68 patients. Acta Orthop Scand. 1996; 67(1):7–9. doi:10.3109/17453679608995599 [CrossRef]
Chen B, Zimmerman JR, Soulen L, DeLisa JA. Continuous passive motion after total knee arthroplasty: a prospective study. Am J Phys Med Rehabil. 2000; 79(5):421–426. doi:10.1097/00002060-200009000-00003 [CrossRef]
Johnson DP. The effect of continuous passive motion on wound-healing and joint mobility after knee arthroplasty. J Bone Joint Surg Am. 1990; 72(3):421–426. doi:10.2106/00004623-199072030-00016 [CrossRef]
Maloney WJ, Schurman DJ, Hangen D, Goodman SB, Edworthy S, Bloch DA. The influence of continuous passive motion on outcome in total knee arthroplasty. Clin Orthop Relat Res. 1990; 256:162–168.
Pope RO, Corcoran S, McCaul K, Howie DW. Continuous passive motion after primary total knee arthroplasty: does it offer any benefits?J Bone Joint Surg Br. 1997; 79(6):914–917. doi:10.1302/0301-620X.79B6.7516 [CrossRef]
Beaupre LA, Davies DM, Jones CA, Cinats JG. Exercise combined with continuous passive motion or slider board therapy compared with exercise only: a randomized controlled trial of patients following total knee arthroplasty. Phys Ther. 2001; 81(4):1029–1037.
Mau-Moeller A, Behrens M, Finze S, Bruhn S, Bader R, Mittelmeier W. The effect of continuous passive motion and sling exercise training on clinical and functional outcomes following total knee arthroplasty: a randomized active-controlled clinical study. Health Qual Life Outcomes. 2014; 12:68. doi:10.1186/1477-7525-12-68 [CrossRef]
Herbold JA, Bonistall K, Blackburn M, et al. . Randomized controlled trial of the effectiveness of continuous passive motion after total knee replacement. Arch Phys Med Rehabil. 2014; 95(7):1240–1245. doi:10.1016/j.apmr.2014.03.012 [CrossRef]
Chen LH, Chen CH, Lin SY, et al. . Aggressive continuous passive motion exercise does not improve knee range of motion after total knee arthroplasty. J Clin Nurs. 2013; 22(3–4):389–394. doi:10.1111/j.1365-2702.2012.04106.x [CrossRef]
Lenssen TA, van Steyn MJ, Crijns YH, et al. . Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty. BMC Musculoskelet Disord. 2008; 9:60. doi:10.1186/1471-2474-9-60 [CrossRef]
Worland RL, Arredondo J, Angles F, Lopez-Jimenez F, Jessup DE. Home continuous passive motion machine versus professional physical therapy following total knee replacement. J Arthroplasty. 1998; 13(7):784–787. doi:10.1016/S0883-5403(98)90031-6 [CrossRef]
Joshi RN, White PB, Murray-Weir M, Alexiades MM, Sculco TP, Ranawat AS. Prospective randomized trial of the efficacy of continuous passive motion post total knee arthroplasty: experience of the Hospital for Special Surgery. J Arthroplasty. 2015; 30(12):2364–2369. doi:10.1016/j.arth.2015.06.006 [CrossRef]
Bennett LA, Brearley SC, Hart JA, Bailey MJ. A comparison of 2 continuous passive motion protocols after total knee arthroplasty: a controlled and randomized study. J Arthroplasty. 2005; 20(2):225–233. doi:10.1016/j.arth.2004.08.009 [CrossRef]
Colwell CW Jr, Morris BA. The influence of continuous passive motion on the results of total knee arthroplasty. Clin Orthop Relat Res. 1992; 276:225–228.
Kumar PJ, McPherson EJ, Dorr LD, Wan Z, Baldwin K. Rehabilitation after total knee arthroplasty: a comparison of 2 rehabilitation techniques. Clin Orthop Relat Res. 1996; 331:93–101. doi:10.1097/00003086-199610000-00013 [CrossRef]
Maniar RN, Baviskar JV, Singhi T, Rathi SS. To use or not to use continuous passive motion post-total knee arthroplasty presenting functional assessment results in early recovery. J Arthroplasty. 2012; 27(2):193–200. doi:10.1016/j.arth.2011.04.009 [CrossRef]
Johnson DP, Eastwood DM. Beneficial effects of continuous passive motion after total condylar knee arthroplasty. Ann R Coll Surg Engl. 1992; 74(6):412–416.
Leach W, Reid J, Murphy F. Continuous passive motion following total knee replacement: a prospective randomized trial with follow-up to 1 year. Knee Surg Sports Traumatol Arthrosc. 2006; 14(10):922–926. doi:10.1007/s00167-006-0042-9 [CrossRef]
Alkire MR, Swank ML. Use of inpatient continuous passive motion versus no CPM in computer-assisted total knee arthroplasty. Orthop Nurs. 2010; 29(1):36–40. doi:10.1097/NOR.0b013e3181c8ce23 [CrossRef]
Boese CK, Weis M, Phillips T, Lawton-Peters S, Gallo T, Centeno L. The efficacy of continuous passive motion after total knee arthroplasty: a comparison of three protocols. J Arthroplasty. 2014; 29(6):1158–1162. doi:10.1016/j.arth.2013.12.005 [CrossRef]
McInnes J, Larson MG, Daltroy LH, et al. . A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty. JAMA. 1992; 268(11):1423–1428. doi:10.1001/jama.268.11.1423 [CrossRef]
Nielsen PT, Rechnagel K, Nielsen SE. No effect of continuous passive motion after arthroplasty of the knee. Acta Orthop Scand. 1988; 59(5):580–581. doi:10.3109/17453678809148789 [CrossRef]
Walker RH, Morris BA, Angulo DL, Schneider J, Colwell CW Jr, . Postoperative use of continuous passive motion, transcutaneous electrical nerve stimulation, and continuous cooling pad following total knee arthroplasty. J Arthroplasty. 1991; 6(2):151–156. doi:10.1016/S0883-5403(11)80010-0 [CrossRef]
Herbold JA, Bonistall K, Blackburn M. Effectiveness of continuous passive motion in an inpatient rehabilitation hospital after total knee replacement: a matched cohort study. PM R. 2012; 4(10):719–725. doi:10.1016/j.pmrj.2012.07.004 [CrossRef]
Oshodi TO. The impact of preoperative education on postoperative pain: Part 2. Br J Nurs. 2007; 16(13):790–797. doi:10.12968/bjon.2007.16.13.24244 [CrossRef]
Oshodi TO. The impact of preoperative education on postoperative pain: Part 1. Br J Nurs. 2007; 16(12):706–710. doi:10.12968/bjon.2007.16.12.23719 [CrossRef]
Hathaway D. Effect of preoperative instruction on postoperative outcomes: a meta-analysis. Nurs Res. 1986; 35(5):269–275. doi:10.1097/00006199-198609000-00004 [CrossRef]
Louw A, Diener I, Butler DS, Puentedura EJ. Preoperative education addressing postoperative pain in total joint arthroplasty: review of content and educational delivery methods. Physiother Theory Pract. 2013; 29(3):175–194. doi:10.3109/09593985.2012.727527 [CrossRef]
Chen SR, Chen CS, Lin PC. The effect of educational intervention on the pain and rehabilitation performance of patients who undergo a total knee replacement. J Clin Nurs. 2014; 23(1–2):279–287. doi:10.1111/jocn.12466 [CrossRef]
Crowe J, Henderson J. Pre-arthroplasty rehabilitation is effective in reducing hospital stay. Can J Occup Ther. 2003; 70(2):88–96. doi:10.1177/000841740307000204 [CrossRef]
Aydin D, Klit J, Jacobsen S, Troelsen A, Husted H. No major effects of preoperative education in patients undergoing hip or knee replacement: a systematic review. Dan Med J. 2015; 62(7):A5106.
Ditmyer MM, Topp R, Pifer M. Prehabilitation in preparation for orthopaedic surgery. Orthop Nurs. 2002; 21(5):43–51. doi:10.1097/00006416-200209000-00008 [CrossRef]
Williamson L, Wyatt MR, Yein K, Melton JT. Severe knee osteoarthritis: a randomized controlled trial of acupuncture, physiotherapy (supervised exercise) and standard management for patients awaiting knee replacement. Rheumatology (Oxford). 2007; 46(9):1445–1449. doi:10.1093/rheumatology/kem119 [CrossRef]
Mitchell C, Walker J, Walters S, Morgan AB, Binns T, Mathers N. Costs and effectiveness of pre- and post-operative home physiotherapy for total knee replacement: randomized controlled trial. J Eval Clin Pract. 2005; 11(3):283–292. doi:10.1111/j.1365-2753.2005.00535.x [CrossRef]
Matassi F, Duerinckx J, Vandenneucker H, Bellemans J. Range of motion after total knee arthroplasty: the effect of a preoperative home exercise program. Knee Surg Sports Traumatol Arthrosc. 2014; 22(3):703–709. doi:10.1007/s00167-012-2349-z [CrossRef]
Beaupre LA, Lier D, Davies DM, Johnston DB. The effect of a preoperative exercise and education program on functional recovery, health related quality of life, and health service utilization following primary total knee arthroplasty. J Rheumatol. 2004; 31(6):1166–1173.
Kwok IH, Paton B, Haddad FS. Does preoperative physiotherapy improve outcomes in primary total knee arthroplasty? A systematic review. J Arthroplasty. 2015; 30(9):1657–1663. doi:10.1016/j.arth.2015.04.013 [CrossRef]
Gill SD, McBurney H. Does exercise reduce pain and improve physical function before hip or knee replacement surgery? A systematic review and meta-analysis of randomized controlled trials. Arch Phys Med Rehabil. 2013; 94(1):164–176. doi:10.1016/j.apmr.2012.08.211 [CrossRef]
Wallis JA, Taylor NF. Pre-operative interventions (non-surgical and non-pharmacological) for patients with hip or knee osteoarthritis awaiting joint replacement surgery: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2011; 19(12):1381–1395. doi:10.1016/j.joca.2011.09.001 [CrossRef]
D’Lima DD, Colwell CW Jr, Morris BA, Hardwick ME, Kozin F. The effect of preoperative exercise on total knee replacement outcomes. Clin Orthop Relat Res. 1996; 326:174–182. doi:10.1097/00003086-199605000-00020 [CrossRef]
Coudeyre E, Jardin C, Givron P, Ribinik P, Revel M, Rannou F. Could preoperative rehabilitation modify postoperative outcomes after total hip and knee arthroplasty? Elaboration of French clinical practice guidelines. Ann Readapt Med Phys. 2007; 50(3):189–197. doi:10.1016/j.annrmp.2007.02.002 [CrossRef]
Pua YH, Ong PH. Association of early ambulation with length of stay and costs in total knee arthroplasty: retrospective cohort study. Am J Phys Med Rehabil. 2014; 93(11):962–970. doi:10.1097/PHM.0000000000000116 [CrossRef]
Zietek P, Zietek J, Szczypior K, Safranow K. Effect of adding one 15-minute-walk on the day of surgery to fast-track rehabilitation after total knee arthroplasty: a randomized, single-blind study. Eur J Phys Rehabil Med. 2015; 51(3):245–252.
Lenssen AF, Crijns YH, Waltjé EM, et al. . Efficiency of immediate postoperative inpatient physical therapy following total knee arthroplasty: an RCT. BMC Musculoskelet Disord. 2006; 7:71. doi:10.1186/1471-2474-7-71 [CrossRef]
Isaac D, Falode T, Liu P, I’Anson H, Dillow K, Gill P. Accelerated rehabilitation after total knee replacement. Knee. 2005; 12(5):346–350. doi:10.1016/j.knee.2004.11.007 [CrossRef]
Doman DM, Gerlinger TL. Total joint arthroplasty cost savings with a rapid recovery protocol in a military medical center. Mil Med. 2012; 177(1):64–69. doi:10.7205/MILMED-D-11-00163 [CrossRef]
Vince KG, Kelly MA, Beck J, Insall JN. Continuous passive motion after total knee arthroplasty. J Arthroplasty. 1987; 2(4):281–284. doi:10.1016/S0883-5403(87)80060-8 [CrossRef]
Lenssen AF, Crijns YH, Waltjé EM, et al. . Effectiveness of prolonged use of continuous passive motion (CPM) as an adjunct to physiotherapy following total knee arthroplasty: design of a randomised controlled trial [ISRCTN85759656]. BMC Musculoskelet Disord. 2006; 7:15. doi:10.1186/1471-2474-7-15 [CrossRef]
Brosseau L, Milne S, Wells G, et al. . Efficacy of continuous passive motion following total knee arthroplasty: a metaanalysis. J Rheumatol. 2004; 31(11):2251–2264.
Milne S, Brosseau L, Robinson V, et al. . Continuous passive motion following total knee arthroplasty. Cochrane Database Syst Rev.2003; 2:CD004260.
He ML, Xiao ZM, Lei M, Li TS, Wu H, Liao J. Continuous passive motion for preventing venous thromboembolism after total knee arthroplasty. Cochrane Database Syst Rev.2014; 7:CD008207.
Harvey LA, Brosseau L, Herbert RD. Continuous passive motion following total knee arthroplasty in people with arthritis. Cochrane Database Syst Rev.2010; 3:CD004260.
Ebert JR, Munsie C, Joss B. Guidelines for the early restoration of active knee flexion after total knee arthroplasty: implications for rehabilitation and early intervention. Arch Phys Med Rehabil. 2014; 95(6):1135–1140. doi:10.1016/j.apmr.2014.02.015 [CrossRef]
Brennan GP, Fritz JM, Houck LT, Hunter SJ. Outpatient rehabilitation care process factors and clinical outcomes among patients discharged home following unilateral total knee arthroplasty. J Arthroplasty. 2015; 30(5):885–890. doi:10.1016/j.arth.2014.12.013 [CrossRef]
Majumdar SS, Luccisano M, Evans C. Perceptions of physiotherapy best practice in total knee arthroplasty in hospital outpatient settings. Physiother Can. 2011; 63(2):234–241. doi:10.3138/ptc.2010-09 [CrossRef]
Naylor JM, Mittal R, Carroll K, Harris IA. Introductory insights into patient preferences for outpatient rehabilitation after knee replacement: implications for practice and future research. J Eval Clin Pract. 2012; 18(3):586–592. doi:10.1111/j.1365-2753.2010.01619.x [CrossRef]
Aprile I, Rizzo RS, Romanini E, et al. . Group rehabilitation versus individual rehabilitation following knee and hip replacement: a pilot study with randomized, single-blind, crossover design. Eur J Phys Rehabil Med. 2011; 47(4):551–559.
Ko V, Naylor J, Harris I, Crosbie J, Yeo A, Mittal R. One-to-one therapy is not superior to group or home-based therapy after total knee arthroplasty: a randomized, superiority trial. J Bone Joint Surg Am. 2013; 95(21):1942–1949. doi:10.2106/JBJS.L.00964 [CrossRef]
Froimson MI. In-home care following total knee replacement. Cleve Clin J Med. 2013; 80(suppl 1):eS15–eS18. doi:10.3949/ccjm.80.e-s1.04 [CrossRef]
Buker N, Akkaya S, Akkaya N, et al. . Comparison of effects of supervised physiotherapy and a standardized home program on functional status in patients with total knee arthroplasty: a prospective study. J Phys Ther Sci. 2014; 26(10):1531–1536. doi:10.1589/jpts.26.1531 [CrossRef]
Rajan RA, Pack Y, Jackson H, Gillies C, Asirvatham R. No need for outpatient physiotherapy following total knee arthroplasty: a randomized trial of 120 patients. Acta Orthop Scand. 2004; 75(1):71–73. doi:10.1080/00016470410001708140 [CrossRef]
Kramer JF, Speechley M, Bourne R, Rorabeck C, Vaz M. Comparison of clinic- and home-based rehabilitation programs after total knee arthroplasty. Clin Orthop Relat Res. 2003; 410:225–234. doi:10.1097/01.blo.0000063600.67412.11 [CrossRef]
Han AS, Nairn L, Harmer AR, et al. . Early rehabilitation after total knee replacement surgery: a multicenter, noninferiority, randomized clinical trial comparing a home exercise program with usual outpatient care. Arthritis Care Res (Hoboken). 2015; 67(2):196–202. doi:10.1002/acr.22457 [CrossRef]
Russell TG, Buttrum P, Wootton R, Jull GA. Internet-based outpatient telerehabilitation for patients following total knee arthroplasty: a randomized controlled trial. J Bone Joint Surg Am. 2011; 93(2):113–120. doi:10.2106/JBJS.I.01375 [CrossRef]
Moffet H, Tousignant M, Nadeau S, et al. . In-home telerehabilitation compared with face-to-face rehabilitation after total knee arthroplasty: a noninferiority randomized controlled trial. J Bone Joint Surg Am. 2015; 97(14):1129–1141. doi:10.2106/JBJS.N.01066 [CrossRef]
Tousignant M, Moffet H, Nadeau S, et al. . Cost analysis of in-home telerehabilitation for post-knee arthroplasty. J Med Internet Res. 2015; 17(3):e83. doi:10.2196/jmir.3844 [CrossRef]
Kittelson AJ, Stackhouse SK, Stevens-Lapsley JE. Neuromuscular electrical stimulation after total joint arthroplasty: a critical review of recent controlled studies. Eur J Phys Rehabil Med. 2013; 49(6):909–920.
Levine M, McElroy K, Stakich V, Cicco J. Comparing conventional physical therapy rehabilitation with neuromuscular electrical stimulation after TKA. Orthopedics. 2013; 36(3):e319–e324. doi:10.3928/01477447-20130222-20 [CrossRef]
Avramidis K, Strike PW, Taylor PN, Swain ID. Effectiveness of electric stimulation of the vastus medialis muscle in the rehabilitation of patients after total knee arthroplasty. Arch Phys Med Rehabil. 2003; 84(12):1850–1853. doi:10.1016/S0003-9993(03)00429-5 [CrossRef]
Demircioglu DT, Paker N, Erbil E, Bugdayci D, Emre TY. The effect of neuromuscular electrical stimulation on functional status and quality of life after knee arthroplasty: a randomized controlled study. J Phys Ther Sci. 2015; 27(8):2501–2506. doi:10.1589/jpts.27.2501 [CrossRef]
Stevens-Lapsley JE, Balter JE, Wolfe P, Eckhoff DG, Kohrt WM. Early neuromuscular electrical stimulation to improve quadriceps muscle strength after total knee arthroplasty: a randomized controlled trial. Phys Ther. 2012; 92(2):210–226. doi:10.2522/ptj.20110124 [CrossRef]
Petterson SC, Mizner RL, Stevens JE, et al. . Improved function from progressive strengthening interventions after total knee arthroplasty: a randomized clinical trial with an imbedded prospective cohort. Arthritis Rheum. 2009; 61(2):174–183. doi:10.1002/art.24167 [CrossRef]
Peter WF, Nelissen RG, Vlieland TP. Guideline recommendations for post-acute postoperative physiotherapy in total hip and knee arthroplasty: are they used in daily clinical practice?Musculoskeletal Care. 2014; 12(3):125–131. doi:10.1002/msc.1067 [CrossRef]
Piva SR, Gil AB, Almeida GJ, DiGioia AM III, Levison TJ, Fitzgerald GK. A balance exercise program appears to improve function for patients with total knee arthroplasty: a randomized clinical trial. Phys Ther. 2010; 90(6):880–894. doi:10.2522/ptj.20090150 [CrossRef]
Fung V, Ho A, Shaffer J, Chung E, Gomez M. Use of Nintendo Wii Fit in the rehabilitation of outpatients following total knee replacement: a preliminary randomised controlled trial. Physiotherapy. 2012; 98(3):183–188. doi:10.1016/ [CrossRef]
McPhail SM, O’Hara M, Gane E, Tonks P, Bullock-Saxton J, Kuys SS. Nintendo Wii Fit as an adjunct to physiotherapy following lower limb fractures: preliminary feasibility, safety and sample size considerations. Physiotherapy. 2016; 102(2):217–220. doi:10.1016/ [CrossRef]
The authors are from the Albert Einstein College of Medicine (MGJ), Bronx, New York; and Stanford University School of Medicine (SB, DFA), Redwood City, California.
Mr Joice and Dr Bhowmick have no relevant financial relationships to disclose. Dr Amanatullah is a paid consultant for Omni, Exactech, Blue-Jay Mobile Health, Stryker, Medscape, and Sanofi and has received grants from BlueJay Mobile Health and Stryker.
Correspondence should be addressed to: Derek F. Amanatullah, MD, PhD, Stanford University School of Medicine, 450 Broadway St, M/C 6342, Pavilion C, 4th Fl, Redwood City, CA 94063 (

Copyright 2017, SLACK Incorporated

Received: June 16, 2016
Accepted: October 31, 2016


23 million Americans to lose health insurance

An estimated 23 million people would lose health coverage by 2026 under Republican legislation aimed at repealing Obamacare, a nonpartisan congressional agency said on Wednesday in the first calculation of the new bill’s potential impact. Chris Dignam reports.

The House Republican healthcare bill passed earlier this month will leave 23 million more Americans without health insurance.

That’s the latest estimate from the U.S. Congressional Budget Office, which released its findings Wednesday afternoon. The new number down minimally from the estimated 24 million people who would lose health insurance by 2026 in the CBO’s score of the previous House bill.

Republicans facing harsh criticism since passing their health bill from Democrats and in town halls across the country. The backlash likely to escalate as the CBO concluded the number of uninsured was only reduced by 1 million people and that premiums will vary significantly.

The report also saying that the bill would cut the federal deficit by 119 billion dollars between now and 2026. That calculation opens the door for Congress to pass the bill through a process called reconciliation, which requires only a simple majority instead of a full two-thirds of votes in the Senate. Republicans hold a 52-48 majority.

Soon after the release of the new CBO score the minority voicing its opposition.


“The report makes clear Trump Care would be a cancer on the American health care system.”

A group of 13 Republican senators led by Mitch McConnell have said they’ll be rewriting their own version of the healthcare bill in the coming months. The majority leader telling Reuters Wednesday: “I don’t know how we get to 50 at the moment. But that’s the goal.”


Balloon capsules can help obese patients lose weight faster

Obese patients who swallowed balloon capsules that helped them eat less lost an average of 15 pounds, roughly two times more weight than patients who just dieted and exercised, researchers report.

obeseThe capsule was inflated with gas via a catheter when it reached the stomach. As many as three balloons were placed over three months, and all of the balloons were removed after six months. The balloons made patients feel full, the researchers explained.

In addition to the balloons, patients followed a moderate diet and behavior modification program. Whether the weight loss will last over the long term isn’t known, said lead researcher Dr. Aurora Pryor, director of the Bariatric and Metabolic Weight Loss Center at Stony Brook University in New York.

The study lasted a year, but “we don’t know what happens after that,” Pryor said.

“If they are able to stick to their newfound lifestyle with their diet and exercise program, they could maintain their weight loss,” she said. “The long-term results are dependent on patients keeping their motivation to stay with their diet and exercise programs.”

The balloon treatment will be available starting in January, but the cost hasn’t been announced, Pryor said. The device, called the Obalon Balloon System, was approved in September by the U.S. Food and Drug Administration.

An advantage of the balloons is that patients have no downtime and can go back to work the same day, the researchers said.

“There is no sedation or recovery time when the balloons are placed, but there is sedation when the balloons are removed, so you wouldn’t want to go back to work after that,” Pryor added.

Pryor believes balloons are a better option for patients who are candidates for weight loss surgery but don’t want surgery. “For people who want to lose some weight but don’t feel they are heavy enough for surgery or they’re afraid of surgery, this is a really good next step to help them jump start their weight loss,” she suggested.

The findings were to be presented Friday at the annual meeting of the American Society for Metabolic and Bariatric Surgery and the Obesity Society in New Orleans. Research presented at meeting is considered preliminary until published in a peer-reviewed journal.

One weight-loss expert expressed some doubts about the findings.

“I still question the efficacy of balloons,” said Dr. Mitchell Roslin, chief of obesity surgery at Lenox Hill Hospital in New York City. “While there is potentially easier insertion that does not require sedation, I still doubt after removal there will be weight loss,” he said.

Roslin said patients who have other treatments that restrict their ability to eat — such as bands and bypass operations that reduce the size of the stomach — often regain lost weight over time. “As time goes on, weight loss will be about lifestyle changes,” he said.

The only argument for the balloon is that it starts the lifestyle changes, Roslin said. “It may make it easier to become motivated,” he said. “But I believe that few will maintain weight loss two years after any balloon.”

For the study, Pryor and her colleagues randomly assigned nearly 400 obese patients to receive a real or sham device. All patients also had 25 minutes of lifestyle therapy every three weeks. After six months, patients with the Obalon balloons had them removed.

During the time patients had the balloons, and for six months after, the researchers monitored their weight loss. The investigators also followed those who had not received the balloon therapy.

People treated with the balloons lost an average of 7 percent of their weight, compared to less than 4 percent for those who received the sham device, the researchers found. Six months after the balloons were removed, nearly 90 percent maintained the weight loss they achieved during treatment, Pryor said.

As for side effects, one patient had a bleeding stomach ulcer while taking high doses of pain pills after a knee replacement. Most patients (91 percent) suffered from stomach cramps and nausea, which nearly 100 percent said were mild or moderate.

The results were also presented at a medical meeting in May.

One health and nutrition expert noted that a balloon does not equal a lifestyle change.

“A gastric balloon may help with weight loss, but will do nothing to improve diet quality and overall health,” said Dr. David Katz. He is director of the Yale-Griffin Prevention Research Center in Derby, Conn., and president of the American College of Lifestyle Medicine.

The role for such technology-based approaches to weight control should be a small one, he said.

“Such devices may be alternatives to bariatric surgery in some cases. But they should not distract us from the far better solution at the population level: practices, programs and policies that make eating well and being active a cultural norm,” Katz said.


Heat stroke

Heat stoke is a very serious medical condition that happens when the body overheats and is unable to cool down without external help. It causes at least 240 deaths in the United States each year, according to the American Academy of Family Physicians.

Causes & symptoms

Heat stroke, a form of hyperthermia, is characterized by a core body temperature of 104 degrees Fahrenheit (40 degrees Celsius) or greater. “When suffering from heat stroke, the body’s natural temperature regulation process is overwhelmed by the external heat,” said Dr. Erik Polan, an internal medicine doctor at Philadelphia College of Osteopathic Medicine. “Organ systems may become damaged due to dehydration and elevated internal temperature, which can be lethal.”

There are two types of heat stroke. One is generally seen in older patients during heat waves. This is known as classical heat stroke (CHS). The other is seen in younger people who are exerting themselves in a hot, humid environment. This type is known as exertional heat stroke (EHS), explained Dr. Neha Raukar, an associate professor of emergency medicine at Brown University.

While EHS comes on quickly, CHS can take two to three days of exposure to heat to develop, according to the Merck Manual.

According to the U.S. National Library of Medicine, heat cramps — usually muscle cramps in the leg or abdomen — are the first sign of heat stroke. Other symptoms include fainting, dizziness, confusion, lightheadedness, fatigue, headache, nausea, vomiting, loss of consciousness and unusual behavior such as aggression. The person may also have hot, dry or red skin, an increased heart rate and/or a change in their breathing.


A person with possible heat stroke must be treated immediately. The extreme heat can damage the heart, brain, kidneys and muscles very quickly. The longer it is left untreated, the worse the damage can become.

“As a neurosurgeon, I feel passionate about raising awareness of EHS, as this condition can cause long-term damage to the brain,” said Dr. Julian Bailes Jr., director of the department of neurosurgery and co-director of the NorthShore University HealthSystem Neurological Institute. “I’ve found that too often, people ignore the warning signs of overheating and their condition turns into a potentially life-threatening medical emergency – EHS – which can threaten organ function or life itself.”

To begin treatment, first call 911, and then move the person to a cooler area, if possible. Remove as much clothing as possible and apply cool, wet cloths to the skin to help lower their body temperature. Applying ice packs to the body is also helpful. If the person is conscious, getting them to drink water is also important.

Once in professional care, medical professionals may immerse the patient in cold water, use evaporation cooling techniques, pack the patient in ice or wrap the body in a cooling blanket. Ice packs may also be applied to the neck, groin, back and armpits to lower the body temperature, according to the Mayo Clinic. Medications to stop any shivering, like muscle relaxants, may also be given to the patient since shivering can raise the body temperature, which is at odds with the goals of the treatment.

After treatment, the patient will be required to stay only in cool areas to prevent a relapse.


It’s important to take preventive measures to avoid heat stroke. “Those most at risk for heat stroke are children, the elderly who may live alone, those with chronic medical issues, and those who participate in strenuous activity outdoors,” said Polan.

Some strenuous activities include mowing the lawn, dancing at concerts and exercising outside. While working or exercising in hot temperatures, wear loose, light clothing to reflect light and help encourage airflow for better sweat evaporation. Also, take regular breaks, stay hydrated and try to schedule outdoor work before 10 a.m. and after 3 p.m. to avoid the hottest part of the day.

Being informed about what medications and substances can contribute to heat stroke is also useful. According to the American Academy of Family Physicians, these include:

  • Alcohol
  • Amphetamines
  • Anticholinergics
  • Antihistamines
  • Benzodiazepines
  • Beta blockers
  • Calcium channel blockers
  • Cocaine
  • Diuretics
  • Laxatives
  • Neuroleptics
  • Phenothiazines
  • Thyroid agonists
  • Tricyclic antidepressants

Don’t forget about helping others. Check in on loved ones and neighbors who are in these high-risk groups, and be particularly mindful of small children — never, ever leave a child unattended in a hot car, even for a moment, advised Polan.

From 1990 to 2016, 793 children died of heat stroke after being left in a hot car. The temperature in a car can rise 20 F (11 C) in 10 minutes when parked in the sun, according to the Mayo Clinic. Even in the shade with the windows cracked, the temperatures in a car on a warm day can become deadly in minutes.


Plant protein may protect against type 2 diabetes, meat eaters might be at greater risk

A new study from the University of Eastern Finland adds to the growing body of evidence indicating that the source of dietary protein may play a role in the risk of developing type 2 diabetes. The researchers found that plant protein was associated with a lower risk of type 2 diabetes, while persons with a diet rich in meat had a higher risk. The findings were published in the British Journal of Nutrition.

Earlier research has linked a high overall intake of protein and animal protein — and eating plenty of processed red meat in particular — with a higher risk of type 2 diabetes. However, the significance of proteins from different sources for the risk of diabetes is an understudied topic, prompting the researchers to analyse the associations of dietary protein with the risk of type 2 diabetes in the Kuopio Ischaemic Heart Disease Risk Factor Study, KIHD, carried out at the University of Eastern Finland. At the baseline of the study in 1984-1989, the researchers analysed the diets of 2,332 men who were between 42 and 60 years of age and who did not have type 2 diabetes at baseline. During a follow-up of 19 years, 432 men were diagnosed with type 2 diabetes.

Replacing animal protein with plant protein can reduce diabetes risk

Men with a high intake of plant protein also had healthy lifestyle habits, but lifestyle habits alone did not explain their lower risk of diabetes. The risk of men with the highest intake of plant protein to develop type 2 diabetes was 35 per cent smaller than the risk of those with the lowest intake of plant protein. Using a computational model, the researchers estimated that replacing approximately 5 grams of animal protein with plant protein daily would reduce the risk of diabetes by 18 per cent. The consumption of plant protein was also associated with lower blood glucose levels at the beginning of the study, which may explain the linkage of plant protein with reduced diabetes risk. In this study, grain products were the main source of plant protein, with other sources being potatoes and other vegetables.

The researchers also discovered an association of a high intake of meat with a higher risk of type 2 diabetes. The strongest association was seen in the consumption of meat in general, including processed and unprocessed red meat, white meat and variety meats. The link between eating meat and having a higher risk of diabetes is likely caused by other compounds found in meat than protein, as meat protein was not associated with the risk of diabetes. The intake of overall protein, animal protein, fish protein or dairy protein were not associated with the risk of type 2 diabetes. The association of egg protein was found to be similar to the research group’s earlier findings relating to the consumption of eggs: a higher intake was associated with a lower risk.

The findings indicate that a diet preferring plant protein may help prevent type 2 diabetes.


Artificial blood transfusions

Blood transfusions can save the lives of patients who have suffered major blood loss, but hospitals don’t always have enough or the right type on hand. In search of a solution, researchers have developed a promising substitute using blood’s oxygen-carrying component, hemoglobin. The in vitro study, reported in ACS’ journal Biomacromolecules, found that the modified hemoglobin was an effective oxygen carrier and also scavenged for potentially damaging free radicals.

Red blood cells are the most commonly transfused component of blood, according to the U.S. National Heart, Lung, and Blood Institute. These cells carry the protein hemoglobin, which performs the essential function of delivering oxygen to the body’s tissues. Scientists have tried developing chemically modified hemoglobin — which by itself is toxic — as a blood substitute but have found that it forms methemoglobin. This form of the protein doesn’t bind oxygen and thus decreases the amount of oxygen that blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage. Hong Zhou, Lian Zhao, Yan Wu and colleagues wanted to see if packaging hemoglobin in a benign envelope could get around these problems.

The researchers developed a one-step method for wrapping hemoglobin in polydopamine, or PDA, which has been widely studied for biomedical applications. A battery of lab tests showed that the PDA-coated hemoglobin effectively carried oxygen, while preventing the formation of methemoglobin and hydrogen peroxide. In addition, it caused minimal cell damage, and acted as an effective antioxidant, scavenging for potentially damaging free radicals and reactive oxygen species.


Past kidney injury may raise risk of poor pregnancy outcomes

The risk of preeclampsia and other pregnancy complications may be greater for expectant mothers who have a history of acute kidney injury, a new study finds, even when kidney function is normal prior to pregnancy.

Study leader Dr. Jessica Sheehan Tangren, of the Division of Nephrology at Massachusetts General Hospital (MGH) in Boston, and colleagues believe that their results indicate it is important for obstetricians to get a clear picture of past kidney health for pregnant women.

The researchers recently published their findings in the Journal of the American Society of Nephrology.

Acute kidney injury (AKI) is the sudden onset of kidney damage or failure. The condition can lead to an accumulation of waste products in the blood, an imbalance of body fluids, and it may also affect the function of other organs, including the brain, heart, and lungs.

According to the National Kidney Foundation, AKI is most common among older adults, but it can also affect children and young adults.

Causes of AKI include severe infections (such as sepsis), vasculitis (inflammation and scarring of the blood vessels), allergic reactions, low blood pressure, and major surgery.

Dr. Tangren and colleagues note that existing kidney disease is known to increase the risk of pregnancy complications for expectant mothers, but previous studies have not investigated how a history of AKI might impact pregnancy outcomes.

Preeclampsia risk 5.9 times greater with history of AKI

With the aim of finding out, the team analyzed the medical records of 24,745 women who gave birth at MGH between 1998-2007. Of these women, 24,640 had no history of kidney disease (the controls), while 105 had a history of AKI, from which they had fully recovered prior to pregnancy.

Compared with women who had no history of kidney disease, those with a history of recovered AKI (r-AKI) were found to be at much greater risk of pregnancy complications.

The rate of preeclampsia – a condition characterized by high blood pressure, swelling, and protein in the urine – was 4 percent for the controls, compared with 23 percent for women with a history of r-AKI.

Babies of women with a history of r-AKI were also more likely to be born earlier than those of the controls, at 37.6 weeks versus 39.2 weeks, respectively, and they were more likely to be born small for their gestational age, at 15 percent versus 8 percent, respectively.

Additionally, the team found that women with previous r-AKI were more likely to have a cesarean delivery than controls, at 40 percent versus 27 percent, respectively.

After adjusting for a number of possible confounding factors, the researchers found that women with a history of r-AKI were at 2.4 times greater risk of any adverse fetal outcome and 5.9 times increased risk of preeclampsia.

The researchers are unable to explain the mechanisms underlying the link between a history of r-AKI and greater risk of poor pregnancy outcomes. However, they say that it is possible for changes in small blood vessels that occur during kidney injury recovery to affect the kidney’s ability to function effectively during pregnancy.

“We know that kidneys undergo major changes during pregnancy, and that sort of ‘renal stress test’ may reveal previously undetected kidney disease in women with a history of acute kidney injury,” notes Dr. Tangren.

Findings highlight importance of past kidney health for pregnant women
While further studies are needed to confirm their findings, the researchers believe the current results indicate that expectant mothers with a history of AKI should be closely monitored throughout their pregnancy.

“Information like this helps obstetric providers know what to be vigilant for in pregnant women with a history of acute kidney injury and indicates that asking about such history is important,” notes study co-author Dr. Jeffrey Ecker, chief of obstetrics and gynecology at MGH.

“Being especially watchful for signs and symptoms of preeclampsia in such patients is one immediate application of this work,” he adds.

“In a longer view, work like this offers important hypotheses for future study. Can interventions in patients with a history of acute kidney injury prevent complications like preeclampsia?

Taking a baby aspirin each day during pregnancy is recommended for some women at high risk for preeclampsia. Should such preventive treatment be used in women with a history of acute kidney injury? Questions like this deserve further thought and study.”

Dr. Jeffrey Ecker


Daily Low-Dose Aspirin May Cut Pancreatic Cancer Risk

There’s evidence that daily low-dose aspirin may decrease the risk of pancreatic cancer, according to a new study.

The Chinese-based study couldn’t prove cause-and-effect. However, “the balance of evidence shows that people who use aspirin to reduce risk for cardiovascular disease or colorectal cancer can feel positive that their use likely also lowers their risk for pancreatic cancer,” said study lead author Dr. Harvey Risch.

He’s professor of epidemiology at the Yale School of Public Health and Yale Cancer Center in New Haven, Conn.

According to the American Cancer Society, about 53,000 Americans will be diagnosed with pancreatic cancer this year, and almost 42,000 will die from the disease. Pancreatic cancer is often a “silent killer” because symptoms do not emerge until the tumor is advanced.

The new study tracked 761 people diagnosed with pancreatic cancer in Shanghai from 2006 to 2011, and compared them to 794 people who didn’t have the cancer.

All the participants were asked about whether they took low-dose aspirin on a regular basis. Almost all who said they took it did so on a daily basis.

Eighteen percent of the non-cancer patients reported regular use of low-dose aspirin compared to 11 percent of the pancreatic cancer patients.

After adjusting their statistics so they wouldn’t be thrown off by various factors, the researchers estimate that aspirin may reduce the already small risk of pancreatic cancer by 46 percent.

However, Risch’s team stressed that the study doesn’t prove that aspirin directly produces a lower risk, and the participants may not have precisely remembered their aspirin intake.

An analysis of other studies found similar results. The researchers examined 18 other studies that had investigated aspirin use and pancreatic cancer risk over the past two decades and found that as aspirin use increased, the risk of pancreatic cancer significantly decreased.

“Pancreatic cancer is relatively rare — just 1.5 percent of U.S. adults will be diagnosed with it at some point during life — and regular aspirin use can cause appreciable complications for some,” Risch said in a news release from the American Association for Cancer Research. “Therefore, a person should consult his or her doctor about aspirin use.”

One oncologist who reviewed the data said Americans should be cautious in interpreting the results.

“This is an interesting study that suggests that regular aspirin use may reduce the incidence of pancreas cancer — in people living in China,” said Dr. Tony Philip, an oncologist at Northwell Health Cancer Institute in Lake Success, N.Y.

“Anything more than that cannot be extrapolated from this study,” he said. “We know the genetics of people in one part of the world is very different from other parts. In addition, we don’t know what else these patients were doing, for example, taking herbal medicine, their family history, or access to medical care.”

Philip said that he wouldn’t suggest daily low-dose aspirin to his patients based on this data alone. But the findings “can be the basis for further work” researching this issue, he added.


How nutritional guideline’s restriction on sugar intake is not based on high quality science

Nutritional guidelines restricting sugar intake are not based on high quality science, finds new study led by McMaster University and The Hospital for Sick Children (SickKids). The paper is published Dec. 19 in the Annals of Internal Medicine.

The research team conducted a systematic review of nine public health guidelines on sugar recommendations, including those by the influential U.S. Dietary Guidelines for Americans and the World Health Organization (WHO) and found that the recommendations for limiting sugar are based on low to very low quality evidence.

“Although our findings question the recommendations from guidelines produced by leading authorities, the findings should not be used to justify high or increased consumption of nutrient-poor, energy-dense foods and beverages like candy and sugar-sweetened beverages,” says Bradley Johnston, principal investigator of the review.

“We know that it is healthy and advisable to limit our sugar intake, the question remains to what degree, and if we are limiting our sugar intake what are we replacing the sugar with?”

Official caps on sugars vary widely, from less than five per cent of total daily calories, as recommended by the WHO, to advice from the Institute of Medicine which suggests the public to limit sugars to less than 25 per cent of total daily calories.

“When respected organizations issue conflicting recommendations it can result in public confusion, and this raises concerns about the quality of the guidelines, and the quality of the evidence that informed the guidelines,” says Johnston. He is an assistant professor in the Department of Clinical Epidemiology and Biostatistics at McMaster University; an assistant professor of health policy, management and evaluation at the University of Toronto; and scientist in Child Health Evaluative Sciences at SickKids.

Johnston uses former “low-fat” guidelines as an example: “For 40 years it was advised to eat a low fat diet and, as a result, the food industry and the public looked for ways to lower fat content in foods. What happened is that the fat was typically replaced by simple carbohydrates which included sugar creating a less than optimal outcome including an associated rise in obesity and diabetes.

“In the case of lowering sugar intake, what is happening is that sugars are often replaced with starches and other food additives like maltodextrine, providing the same calorie count, but often accompanied by an increased glycemic index (and blood glucose levels).”

The research team identified problems with the nutritional guidelines and in particular problems with the research that supported the guidelines’ recommendations such as; the inclusion of imprecise or small studies; a high risk of bias from uncontrolled studies; the use of outcome measures such as “nutrient displacement, tooth decay and limited weight gain” that are of lower priority to the public, compared to arguably more important outcomes such as obesity and diabetes; a lack of transparency regarding financial conflicts of interest among groups members who developed the guidelines, and a failure to include patient and public representatives in the panels drawing up the guidelines.

Co-first author, Behnam Sadeghirad, a McMaster PhD student in health research methodology, said “At present, there does not appear to be reliable evidence indicating that any of the recommended daily caloric thresholds for sugar intake are strongly associated with negative health effects. The results from this review should be used to promote improvement in the development of trustworthy guidelines on sugar intake.”


Does loss in sleep increase your desire for sugar and fatty foods?

It is not well understood what role sleep loss plays in affecting areas of the brain that control the desire to consume unhealthy foods. A new paper published on December 6 in the journal eLife finds that rapid eye movement (REM) sleep loss leads to increased consumption of unhealthy foods, specifically sucrose and fat. The researchers at the University of Tsukuba’s International Institute for Integrative Sleep Medicine (IIIS) used a new method to produce REM sleep loss in mice along with a chemical-genetic technique to block prefrontal cortex neurons and the behaviors they mediate. As a result, the IIIS researchers discovered that inhibiting these neurons reversed the effect of REM sleep loss on sucrose consumption while having no effect on fat consumption.

REM sleep is a unique phase of sleep in mammals that is closely associated with dreaming and characterized by random eye movement and almost complete paralysis of the body. The prefrontal cortex plays a role in judging the palatability of foods through taste, smell and texture. Moreover, persons who are obese tend to have increased activity in the prefrontal cortex when exposed to high calorie foods. “Our results suggest that the medial prefrontal cortex may play a direct role in controlling our desire to consume weight promoting foods, high in sucrose content, when we are lacking sleep,” says Kristopher McEown, the lead author on this project.


Molecular insights into anti-tumor effects of diabetes drug

Researchers have uncovered a previously unknown molecular mechanism that works at the cell level to help protect the epithelial tissue that lines various body cavities and organs in the body. The discovery may help explain why the widely prescribed diabetes drug metformin appears to preserve the epithelial barrier’s ability to ward off infection, resist inflammation, and suppress tumors.

The team – from the University of California-San Diego School of Medicine – reports the findings in the journal eLife.

The study concerns cells of the epithelium, one of the four main tissue types of the human body – the others are connective, muscle, and nerve tissue. The epithelium lines various cavities and organs and covers flat surfaces.

There is a feature common to nearly all cells called polarity – the asymmetric organization of internal components and shape.

Without this “knowing which way is up” feature, epithelial cells cannot carry out specialized functions, such as maintaining a protective barrier against toxins, disease-causing agents, and triggers of inflammation.

Loss of epithelial cell polarity can cause a breach in the barrier that leads to organ dysfunction and development of tumors.

The new study identifies a previously unknown mechanism that helps strengthen the structure and tight junctions between epithelial cells so they can maintain the barrier.

Metformin activates LKB1-AMPK stress-polarity pathway

Previous studies have shown that the widely prescribed diabetes drug metformin helps preserve the epithelial barrier’s ability to resist stressors such as inflammation, sepsis, low oxygen (hypoxia), and harmful microbes. It also appears to help the barrier suppress tumors.

Other studies published some 10 years ago also uncovered a “stress-polarity” pathway that is only activated when the epithelial cells come under stress.

The pathway is switched on when an enzyme called AMPK – that protects cellular polarity under conditions of stress – is triggered by a tumor suppressor molecule called LKB1.

Senior author Pradipta Ghosh, professor in the departments of Medicine and Cellular and Molecular Medicine, describes LKB1 as a “bona fide tumor suppressor,” mutations in which have been linked to cancers and loss of cell polarity.

For the past 10 years, the question of how the energy-sensing LKB1-AMPK pathway maintains cell polarity during stress has remained unanswered.

However, in the meantime, it has come to light that metformin – a front-line treatment for type 2 diabetes – is an activator of the LKB1-AMPK pathway.

Metformin acts via GIV phosphorylation

In their new study, Prof. Ghosh and colleagues investigated the mechanisms involved in the tumor-suppressive effect of metformin on the LKB1-AMPK pathway.

They discovered that the pathway depends on a key effector – a triggering molecule – of AMPK, a protein called GIV/Girdin.

GIV/Girdin is itself activated by a process called “phosphorylating” (the chemical addition of a phosphate group).

Using cultured polarized epithelial cells, the team showed much of the beneficial effect of metformin on AMPK occurred via phosphorylating GIV and directing it to the tight junctions of the epithelial layer.

In another set of experiments, the researchers found the beneficial effects of metformin activating AMPK virtually disappeared in the absence of GIV phosphorylation. This also resulted in a “leaky” epithelial barrier that eventually collapsed.

Finally, the researchers showed that mutant forms of GIV found in colon cancer that prevent its phosphorylation by AMPK led to tumor cell growth.

“In summary, by identifying GIV/Girdin as a key layer within the stress-polarity pathway we’ve peeled another layer of the proverbial onion. In the process, we’ve provided new insights into the epithelium-protecting and tumor-suppressive actions of one of the most widely prescribed drugs, metformin, which may inspire a fresh look and better designed studies to fully evaluate the benefits of this relatively cheap medication.”

Prof. Pradipta Ghosh


Liver cancer may be linked to chronic sleep desruption

Liver cancer rates have tripled since the 1980s. Researchers now show that persistent sleep deprivation in mice causes liver disease and eventually leads to liver cancer.

The study, by a team from Baylor College of Medicine in Texas, is published in the journal Cancer Cell.

“Recent studies have shown that more than 80 percent of the population in the United States adopt a lifestyle that leads to chronic disruption in their sleep schedules,” notes Loning Fu, senior author of the study and associate professor at Baylor College of Medicine.

“This has also reached an epidemic level in other developed countries, which is coupled with the increase in obesity and liver cancer risk,” she adds.

“Liver cancer is on the rise worldwide, and in human studies we’ve now seen that patients can progress from fatty liver disease to liver cancer without any middle steps such as cirrhosis,” says co-lead author David Moore, professor of molecular and cellular biology.

“We knew we needed an animal model to examine this connection, and studies in the Fu Lab found that chronically jet-lagged mice developed liver cancer in a very similar way as that described for obese humans,” he adds.

Sleep disruption and liver cancer
The “master clock” in our brain regulates the circadian rhythms in tissues and organs around the body. This is important for sleep but also for normal metabolic function.

Shift work has already been linked to disruption of normal circadian function. A study reported by Medical News Today earlier this year, for example, linked simulated shift working patterns in mice with increased development of nonsmall cell lung cancer.

Now, researchers have associated sleep disruption with increased risk of liver cancer.

The American Cancer Society report that 700,000 people worldwide are diagnosed with liver cancer each year. Men are more likely to develop liver cancer than women. In the U.S., they estimate that over 18,000 men and nearly 9,000 women will die in 2016 from liver cancer.

Obesity is a major risk factor for hepatocellular carcinoma (HCC) – the most common type of liver cancer. Excess fat in the liver results in nonalcoholic fatty liver disease (NAFLD), which has a high incidence rate in obese individuals. NAFLD has been predicted to become the major cause of HCC in the 21st century.

Jet-lagged mice developed liver cancer, HCC
To model the effect of chronic sleep disruption – or “social jet lag,” as the team describes it – mice were exposed to disrupted light and dark cycles for nearly 2 years, which resulted in prolonged disruption to their normal sleep cycles.

As a result, the mice developed a range of conditions, including skin disorders, neurodegeneration, and cancer. These were not seen in control mice, which had regular light and dark cycles. All mice received a normal diet.

Both male and female mice developed HCC by the age of 78 weeks, although, as in humans, the rates were much higher in males. Week 78 is equivalent to 67-72 years in human, which is when spontaneous development of HCC is mostly observed.

By the age of 90 weeks, 96 percent of jet-lagged mice had NAFLD, while almost 9 percent developed HCC around the same age.

Normal liver function was severely disrupted in the jet-lagged mice. Development of NAFLD was accompanied by severe inflammation and fibrosis prior to development of HCC.

Rodent gene expression patterns comparable to humans with HCC
When the researchers investigated global gene expression in the livers of jet-lagged mice, they found a pattern similar to that seen in humans with HCC.

This shows the direct effect that chronic jet lag has on gene expression, including genes involved in regulation of circadian rhythm (Bmal1, Clock, Per1, Per2 and Nr1d1), despite a lack of mutations in classic cancer genes.

Cholesterol and bile acid pathways, which are essential for normal liver function, were also disrupted. Nuclear receptor CAR, which is involved in sensing toxic compounds, was constitutively activated, while FXR, the bile acid receptor, was suppressed. This pattern is similar to HCC in humans.

“To us, our results are consistent with what we already knew about these receptors, but they definitely show that chronic circadian disruption alone leads to malfunction of these receptors.” Fu explains. “And thus, maintaining internal physiological homeostasis is really important for liver tumor suppression.”

The team concludes that HCC caused by disruption of normal liver function could be addressed by drugs which target these receptors.

“This experiment allowed us to take several threads that were already there and put them together to come to this conclusion. We think most people would be surprised to hear that chronic jet lag was sufficient to induce liver cancer.”

David Moore


High blood pressure: Global total almost doubles in 4 decades

The largest study of its kind reveals that the number of people worldwide living with high blood pressure has nearly doubled in the last 4 decades. The huge international effort also reveals a stark contrast between rich and poor countries.

The number of people living with high blood pressure, or hypertension, worldwide has grown from 594 million in 1975 to over 1.1 billion in 2015 – mainly because of population growth and aging – says the study, published in The Lancet.

However, while average blood pressure is high and rising in less affluent countries, especially in south Asia and sub-Saharan Africa, it has dropped to an all-time low in high-income nations like Canada, the United Kingdom, and the United States.

The authors say the reason for this contrast is not clear, but they suggest a major factor could be that people in wealthier nations enjoy better health overall and eat more fruits and vegetables.

Earlier diagnosis and control of hypertension is also more likely to occur in wealthier countries. Taken together, these factors also help reduce obesity, another risk factor for high blood pressure.

Childhood nutrition could be another reason, suggests Majid Ezzati, a senior author of the study and a professor at the School of Public Health at Imperial College London in the U.K., who notes:

“Increasing evidence suggests poor nutrition in early life years increases risk of the high blood pressure in later life, which may explain the growing problem in poor countries.”

High blood pressure major global killer

Blood pressure is the pressure of the blood in the blood vessels. It is assessed from two numbers measured in millimeters of mercury (mmHg): systolic pressure and diastolic pressure.

High blood pressure is defined as 140 mmHg systolic and 90 mmHg diastolic pressure or higher. This is normally shown as 140/90 mmHg.

Recent research suggests that the risk of death from cardiovascular diseases like ischemic heart disease and stroke doubles with every 20 mmHg systolic or 10 mmHg diastolic increase in people of middle age and older.

“High blood pressure is the leading risk factor for stroke and heart disease, and kills around 7.5 million people worldwide every year,” says Prof. Ezzati.

The condition is caused by various factors, he and his colleagues note in their paper.

These include diet (for example, eating too much salt and not enough fruit and vegetables), obesity, lack of physical activity, plus environmental factors – such as air pollution and lead exposure.

‘Major health issue linked to poverty’

For the research, the World Health Organization (WHO) teamed up with hundreds of scientists from all over the globe and looked at changes in blood pressure in every country in the world from 1975-2015.

They pooled and analyzed data from nearly 1,500 population-based measurement studies involving a total of 19 million participants.

This showed that of the whole world, South Korea, the U.S., and Canada have the lowest proportion of people with high blood pressure. The U.K. had the lowest in Europe.

The research also shows that in most countries, there are more men with high blood pressure than women. Worldwide, there are 597 million men with high blood pressure, compared with 529 million women.

The figures for 2015 show that more than half of adults with high blood pressure in the world live in Asia, including 226 million in China and 200 million in India.

Prof. Ezzati says high blood pressure is no longer a problem associated with wealthy countries but with poor countries. He says their findings show it is possible to achieve substantial reductions in rates of high blood pressure – as seen in the data from more affluent countries over the last 4 decades. He adds:

“They also reveal that WHO’s target of reducing the prevalence of high blood pressure by 25 percent by 2025 is unlikely to be achieved without effective policies that allow the poorest countries and people to have healthier diets – particularly reducing salt intake and making fruit and vegetables affordable – as well as improving detection and treatment with blood pressure lowering drugs.”

“High blood pressure is no longer related to affluence – as it was in 1975 – but is now a major health issue linked with poverty.”

Prof. Majid Ezzati


Prenetal stress alters gut bacteria causing problems in offspring

Growing body of research suggests that prenatal stress has a long-lasting impact on an infant’s development. A new study adds to the evidence, showing that prenatal stress can negatively affect the child well into adulthood, through a connection via the maternal gut bacteria.

According to an analysis conducted by the Centers for Disease Control and Prevention (CDC), prenatal stress is associated with preterm birth, low birth weight, as well as prenatal and postpartum depression and anxiety in the mother.

An overview of existing research further supports the “fetal origins hypothesis,” according to which prenatal environmental factors can have lifelong effects on the brain development and behavior of offspring.

Pregnant women’s exposure to a variety of stressors, ranging from common to traumatic, have been linked to significant modifications in the children’s neurodevelopment. Stressors such as the loss of a loved one, daily hassles, or financial worries have been connected to autism, affective disorders, and reduced cognitive ability in children.

New research in mice suggests that prenatal exposure to a mother’s stress may change the microbiome in a way that negatively affects the baby.

Gut bacteria and mental health
Tamar Gur, assistant professor of psychiatry, behavioral health, neuroscience, and obstetrics and gynecology at Ohio State University, believes the bacteria to be a particularly good medium for researching the connection between a mother and her fetus.

This is why she led a team of researchers to examine exactly how maternal stress affects the offspring. “We already understand that prenatal stress can be bad for offspring, but the mystery is how,” says Gur, who is also a member of Ohio State Wexner Medical Center’s Institute for Behavioral Medicine Research.

Gur explains that the microbes from a mother’s gastrointestinal and reproductive tracts are the first ones to spread to the developing fetus and the newborn. As a result, gut bacteria might provide an explanation for why and how maternal stress can affect a person’s mental health for their entire life.

“More and more, doctors and researchers understand that naturally occurring bacteria are not just a silent presence in our body, but that they contribute to our health,” says Gur.

How prenatal stress affects offspring in mice
For the study, researchers compared two groups of pregnant mice. One group was subjected to 2 hours of stress-inducing restraint per day for 7 days. The other group was left undisturbed during pregnancy. The gut bacteria of both groups assessed by taking fecal samples.

Researchers found increased markers of inflammation in the placenta, the fetal brain, and the adult brain of the mice’s offspring. The scientists also found a decrease in a supportive protein called the “brain-derived neurotrophic factor.”

When stressed, pregnant mice displayed a change in their bacterial makeup. These changes could be observed both in the mothers’ guts and in the placentas, as well as in the intestines of their female offspring. Bacterial changes lasted all the way into adulthood.

Affected adult mice “were more anxious, they spent more time in dark, closed spaces and they had a harder time learning cognitive tasks even though they were never stressed after birth,” Gur explains.

Researchers found a lower ability to learn and behavior indicative of higher levels of anxiety among the female offspring of the mice. According to Gur, the team found alterations in the behavior of male offspring as well, but the details of that part of the study are still a work in progress.

Gur recently presented the study at Neuroscience 2016 – the annual meeting of the Society for Neuroscience, held in San Diego, CA.

Future research to uncover link between brain and bacteria
The author emphasizes that by no means do the findings suggests mothers should be blamed for their children’s adult mental health. Rather, the results of the study highlight the importance of having a discussion about mental health for both the pregnant mother and the baby.

“As a psychiatrist who treats pregnant women, if you’re stressed, anxious or depressed, I think pregnancy is a prime time for intervention. And what’s good for mom is good for the baby.”

Tamar Gur

In the future, Gur and team hope to further study the link between the brain and the gut bacteria by examining pregnant women and their babies.

Ultimately, Gur hopes to investigate the role of probiotics in alleviating the negative effects of stress.