High-Intensity Interval Training as an Efficacious Alternative to Moderate-Intensity Continuous Training for Adults with Prediabetes

Mary E Jung
School of Health and Exercise Sciences
University of British Columbia
Okanagan Campus
3333 University WayV1V 1V7KelownaBCCanada

Jessica E Bourne
School of Health and Exercise Sciences
University of British Columbia
Okanagan Campus
3333 University WayV1V 1V7KelownaBCCanada

Mark R Beauchamp
School of Kinesiology
University of British Columbia
University Boulevard
210-6081, V6T 1Z1VancouverBCCanada

Emily Robinson
School of Health and Exercise Sciences
University of British Columbia
Okanagan Campus
3333 University WayV1V 1V7KelownaBCCanada

Jonathan P Little
School of Health and Exercise Sciences
University of British Columbia
Okanagan Campus
3333 University WayV1V 1V7KelownaBCCanada

High-Intensity Interval Training as an Efficacious Alternative to Moderate-Intensity Continuous Training for Adults with Prediabetes
10.1155/2015/191595Received 18 October 2014; Accepted 15 February 2015 Academic Editor: Hiroshi OkamotoResearch Article Correspondence should be addressed to Mary E. Jung; firstname.lastname@example.com
Aims. High-intensity interval training (HIIT) leads to improvements in various markers of cardiometabolic health but adherence to HIIT following a supervised laboratory intervention has yet to be tested. We compared self-report and objective measures of physical activity after one month of independent exercise in individuals with prediabetes who were randomized to HIIT ( = 15) or traditional moderate-intensity continuous training (MICT, = 17). Method. After completing 10 sessions of supervised training participants were asked to perform HIIT or MICT three times per week for four weeks. Results. Individuals in HIIT (89 ± 11%) adhered to their prescribed protocol to a greater extent than individuals in MICT (71 ± 31%) as determined by training logs completed over one-month follow-up ( = 0.05, Cohen's d = 0.75). Minutes spent in vigorous physical activity per week measured by accelerometer were higher in HIIT (24 ± 18) as compared to MICT (11 ± 10) at one-month follow-up ( = 0.049, Cohen's d = 0.92). Cardiorespiratory fitness and systolic blood pressure assessed at one-month follow-up were equally improved ( 's < 0.05).Conclusions. This study provides preliminary evidence that individuals with prediabetes can adhere to HIIT over the short-term and do so at a level that is greater than MICT.

Introduction

It is estimated that ∼35% of all US adults have prediabetes and are therefore at high risk for future development of type 2 diabetes (T2D) and cardiovascular disease (CVD, [1]). Regular exercise can help prevent the progression of prediabetes to T2D [2]. Landmark trials, including the Diabetes Prevention Program, have shown that a lifestyle intervention including 150 minutes of moderate-intensity physical activity (primarily walking) per week can reduce the incidence of T2D by ∼58% [3]. These findings have contributed to the development of physical activity guidelines in several countries, which typically recommend at least 150 minutes per week of moderate-intensity activity to improve health [4][5][6]. Unfortunately, the vast majority of individuals fail to achieve this target. Specifically, large population-based studies in the US [7], UK [8], and Canada [9] that objectively measure physical activity by accelerometer suggest that only 15-20% of adults accumulate 150 minutes of moderate-intensity physical activity per week. Alternative forms of physical activity that can increase exercise adherence may therefore be attractive for the prevention of T2D.

High-intensity interval training (HIIT) involves brief bursts of vigorous exercise separated by periods of rest or recovery. HIIT has garnered attention in recent years because it promotes cardiometabolic adaptations that are often superior to moderate-intensity continuous training (MICT) across a range of clinical populations [10,11]. The benefits of HIIT are intriguing because adaptations to HIIT appear to occur with considerably less exercise time commitment than traditional exercise guidelines [12]. For example, time-efficient HIIT has been shown to rapidly improve glucose control in individuals with prediabetes [13,14] and T2D [12,15]. Despite the evidence for promising health benefits in individuals with prediabetes (for review see [16,17]) and suggestions that HIIT may represent a timeefficient health promoting exercise strategy [18], there are no studies that have assessed adherence to HIIT in individuals at high risk for developing T2D.

Epidemiological data suggests that more vigorousintensity physical activity may confer greater benefits to metabolic health [19]. In support of the efficacy of highintensity exercise, the American College of Sports Medicine and American Heart Association guidelines for maintaining fitness and health recommend 150 minutes of moderate or 75 minutes of vigorous physical activity for optimal health. These recommendations imply that equivalent health benefits are achieved in less time, provided the intensity of exercise is high. Advocating this lower volume of vigorous physical activity is of potential importance for exercise adherence as "lack of time" is the most commonly cited perceived barrier to regular exercise participation [20]. However, suggestions of prescribing vigorous-intensity physical activity for health promotion and T2D prevention have been met with reluctance in the scientific, medical, and lay communities, as it is presumed to be too intense and aversive (and thus less likely to be adhered to) for individuals who are sedentary and/or at increased risk of chronic disease [21,22]. By virtue of the built-in rest periods and break in monotony, HIIT is different than high-intensity continuous exercise and may represent an alternative and more feasible option for introducing vigorous activity for health promotion in individuals with prediabetes. In fact, we have recently shown that a majority of inactive adults ( = 44) prefer HIIT (62%) to MICT (20%) and high-intensity continuous training (3%) after experiencing a single bout of each type of exercise [23].

The objective of this feasibility study was to determine the utility of HIIT as an exercise strategy for promoting short-term exercise adherence in comparison to traditional MICT. Individuals with prediabetes were randomized to a two-week supervised exercise intervention involving either HIIT or MICT. After the supervised phase, they were prescribed to maintain, on their own, thrice-weekly exercise sessions of their respective modality. The primary outcome was exercise adherence assessed by accelerometer and training logs after one month of independent exercise. As this preliminary pilot study was the first to examine independent exercise adherence to HIIT in comparison to traditionally prescribed MICT, the time point of one month was chosen a priori because it was deemed important to ascertain the feasibility of prescribing HIIT prior to conducting longer-term adherence trials. A secondary objective was to compare fitness and anthropometric changes in response to HIIT or MICT to determine which type of exercise might lead to greater cardiometabolic benefits. We hypothesized that HIIT would lead to greater adherence and improvements in cardiometabolic risk when compared to MICT.

Materials and Methods

Participants.

Participants with prediabetes between the ages of 30 and 60 years were recruited from posters, online message boards, and word of mouth. After expressing interest, a phone interview was conducted to assess preliminary eligibility. Participants were considered to have prediabetes based on one of the following criteria: (1) physician-diagnosed, (2) HbA1c values between 5.7 and 6.4% (American Diabetes Association [24]) assessed using a clinically validated point-of-care monitor (HbA1c Now, Bayer Inc., Ontario, Canada), (3) fasting blood glucose of 5.6-6.9 mmol/L [24], and/or (4) a CANRISK questionnaire score of moderate/high (>21 [25]). To be eligible, participants also had to be inactive based on completion of less than two 30-minute bouts of moderate-intensity physical activity per week over the past six months. Participants completed the Canadian Society for Exercise Physiology (CSEP) Physical Activity Readiness Questionnaire-Plus (PAR-Q+ [26]) and were cleared for participation in vigorous activity by a CSEP Certified Exercise Physiologist. Exclusion criteria included diagnosed diabetes, glucose lowering medications, uncontrolled hypertension (blood pressure > 160/90), history of heart disease, previous myocardial infarction or stroke, and any contraindications to exercise. Thirty-two participants met the eligibility criteria and were enrolled in the study after providing written informed consent. Flow of participants is depicted in Figure 1.

Procedures.

The study design was approved by the Institutional Clinical Research Ethics Board. Following baseline testing (including accelerometry, cardiorespiratory fitness, blood pressure, and anthropometrics), eligible participants were randomized to HIIT or MICT conditions involving ten sessions of exercise performed over a 12-day period (i.e., Monday-Friday over two weeks with Saturday and Sunday as rest days). Exercise prescriptions for each condition were progressive in nature and were designed to be matched for external work [13]. Specifically, individuals randomized to HIIT began with four intervals lasting 1 minute each at an intensity that elicited ∼90% peak heart rate (HRpeak) separated by 1-minute of low intensity recovery and increased to 10 × 1 min intervals by day 10, which was based on previously published studies in individuals with, and at risk for, T2D [12,13,15]. A 3-minute warm-up and 2-minute cooldown was incorporated into the HIIT sessions. Individuals randomized to MICT began with 20 minutes of continuous activity at ∼65% HRpeak and gradually increased duration to 50 minutes by day 10. Participants self-selected exercise modality (walking outdoors, elliptical machine, treadmill walking, or stationary cycling) for each bout to encourage autonomy. Two trained research assistants (RAs) supervised participants during the training phase. To decrease reliance on staff and encourage the practice of independent exercise, participants completed 3 of the 10 training days (days 4, 7, and 9) at home unsupervised. Participants wore a heart rate monitor during each exercise session (supervised and unsupervised) to monitor exercise intensity and ensure compliance. In addition, participants recorded their exercise bouts in a logbook on both lab and home training days. Participants in both groups received 10 minutes of behavioural counselling each day they trained in the lab (for a total of 70 minutes). The aim of this one-on-one counselling was to further prepare participants for transition from labbased training to independent exercise. The behavioural counselling was grounded in social cognitive theory [27] and identical in content for both conditions. Topics covered during counselling included overcoming exercise barriers, bolstering self-regulatory self-efficacy, planning, and increasing awareness for the physical and psychological benefits of exercise. Taken together, the short-term intervention served to introduce participants to their assigned exercise modality (HIIT or MICT) while providing evidence-based strategies and skills in attempts to bolster continual exercise adherence.

During the supervised training phase, average HRpeak during HIIT (including rest intervals, warm-up, and cooldown) was 82 ± 3% HRpeak, confirming that HIIT sessions were in the vigorous domain. Average HRpeak during MICT was 67 ± 5%, confirming that MICT sessions were in the moderate domain. Following the supervised training phase, participants were instructed to maintain HIIT or MICT three days per week independently. Specifically, individuals randomized to HIIT were prescribed three exercise sessions per week involving 10 × 1-minute intervals at an interval intensity of ∼90% HRpeak separated by 1 minute of easy recovery with a 3-minute warm-up and 2-minute cool down (for a total of 25 minutes of vigorous exercise), while participants randomized to MICT were prescribed three sessions per week of 50minute continuous exercise at an intensity of ∼65% HRpeak. Therefore, the HIIT group was prescribed vigorous exercise requiring 75 minutes of time commitment per week whereas the MICT group was prescribed 150 minutes of moderate activity per week. Training logs were provided and participants were instructed to estimate exercise intensity based on physiological cues and ratings of perceived exertion (RPE) taught during supervised training days. Accelerometers were used to objectively measure physical activity over seven days after four weeks of independent exercise. Adherence was assessed based on accelerometers and training logs.

Measures

2.3.1. Heart Rate. During the supervised training intervention, heart rate was recorded using downloadable Polar heart rate monitors (Polar FT7, Finland) to ensure that participants were working at the prescribed exercise intensity.

Training Logbooks.

Participants were provided with a training logbook to complete during the intervention as well as during the subsequent four weeks of independent exercise. Participants were asked to record (a) the activity performed, (b) the minutes spent engaging in the activity, (c) the number of intervals conducted (for the HIIT condition exclusively), and (d) how hard the session was (RPE, CR-10 scale, [28]) for the session. Training logbooks were returned at the four-week follow-up and were analyzed by calculating the percentage adherence (i.e., number of exercise sessions divided by the number of prescribed sessions times 100% [29]) and average RPE.

Accelerometers.

The Actigraph GT1M accelerometer (Actigraph, LCC, Fort Walton Beach, FL, USA) was used to objectively measure physical activity. This device is a dual-axis motion sensor that records vertical and horizontal accelerations allowing researchers to identify time spent in various physical activity intensities on a daily basis. Participants were instructed to wear the accelerometer for all waking hours of the day and to only remove it for sleeping or water-based activities. The monitor was worn on, or just above, their right hip for seven consecutive days prior to the intervention (baseline) and after 4 weeks of independent exercise. Accelerometer data were also collected during the intervention (days 7, 8, and 9) as a manipulation check. Each time participants wore an accelerometer, they were also asked to monitor their wear time with a self-report log.

Epoch lengths were specified at 5 seconds and were summed as counts per minute. Valid wear time was ascertained using Choi and colleagues [30] parameters (i.e., nonwear is classified as 90 minutes of consecutive zeros, allowing for nonzero counts up to 2 minutes, if no counts are detected during the 30-minute counts before and after this interval). A trained researcher verified valid wear time using the raw data and self-report logs. Freedson et al. [31] cut-points were used to identify time spent in moderate (≥1,952 counts/min), vigorous (≥5,725 counts/min), and moderate-to-vigorous physical activity (MVPA, sum of moderate and vigorous) during wear time on valid days (i.e., ≥10 hours of wear time per day, without any excessive counts ≥20,000 counts/min).

Purposeful exercise was operationalized as minutes spent in MVPA in bouts of at least 10 minutes (MVPA10+ [31]) based on physical activity guidelines, which specify bouts, should be accumulated in bouts of 10 minutes or more. MVPA10+ is a more appropriate measure of purposeful exercise [32] and therefore allows a more direct objective assessment of exercise adherence. Participants were required to have at least 3 valid days to be included in the analyses at baseline and one month [33]. Time spent in moderate activity and vigorous activity, total MVPA, and MVPA10+ were calculated for each valid day independently. Time spent in the various intensities was averaged across valid wear days and multiplied by seven to provide a weekly estimate of physical activity at baseline and one-month follow-up.

Cardiorespiratory Fitness.

Participants performed a continuous incremental ramp maximal exercise test on an electronically braked cycle ergometer (Lode Excalibur, Netherlands) before intervention and at one-month followup to determine peak oxygen uptake (VO 2peak ), HRpeak, and peak power output ( peak ). Expired gas was collected continuously by a metabolic cart (Parvomedics TrueOne 2400, Salt Lake City, Utah, USA) that was calibrated with gases of known concentration and a 3.0 L syringe prior to every test. The test started at 50 Watts and increased by 15 Watts/min. Verbal encouragement was provided to participants throughout the test, which was terminated upon volitional exhaustion or when revolutions per minute fell below 50. VO 2peak was defined as the highest 30 sec average for VO 2 (in L/min and mL/kg/min). Criteria for achieving VO 2peak were (i) respiratory exchange ratio >1.15; (ii) plateau in VO 2 ; (iii) reaching age-predicted HRpeak (220age); and/or (iv) volitional exhaustion.

Anthropometrics and Blood

Pressure. Body mass, height (SECA, 700 SECA, Hamburg, Germany), waist circumference (WC, measured at the level of the umbilicus [34]), and blood pressure (BP [35]) were measured in the morning after an overnight fast at baseline testing and one-month follow-up using standard procedures.

Analytical

Plan. Data were analyzed using SPSS Statistics (v22, 2013) on a per-protocol basis. Independent samples -tests were conducted to examine differences between the two exercise conditions on (a) percentage adherence to the exercise prescription and (b) total number of minutes of purposeful physical activity, reported over the four weeks of independent exercise in the training logbooks. Analyses of covariance (ANCOVA) were conducted to examine differences in accelerometer-derived moderate physical activity, vigorous physical activity, total MVPA, and MVPA10+ between the conditions during the fifth week of independent exercise, after controlling for baseline measures as covariates. In order to examine changes in cardiorespiratory fitness, anthropometry, and blood pressure between baseline and one-month follow-up, a series of two-way (group × time) repeated measures ANOVA were conducted. Independent sample -tests were conducted prior to running the repeated measures ANOVA to ensure there were no differences in baseline activity levels or fitness data between conditions. Significance was set at ≤ 0.05.

Results

All 32 participants (17 in MICT, 15 in HIIT) completed the short-term supervised intervention with no complications (see Figure 1 for participation flow through the study). Descriptive statistics for these individuals are provided in Table 1. One participant in MICT did not return for onemonth testing and was deemed lost to follow-up as she could not be reached after repeated attempts to contact. The remaining 16 MICT participants returned for 1-month followup. In the HIIT condition, all 15 participants completed the 2week intervention. At one-month follow-up, two participants were deemed lost to follow-up and did not provide specific reasons. Three participants were unable to complete onemonth follow-up for reasons unrelated to the study (car accident, work-related injury, diagnosis of depression, and change in medication). Therefore, a total of 16 and 10 participants completed one-month follow-up for MICT and HIIT, respectively. Of the individuals that completed one-month follow-up, accelerometer data were available for 10 individuals in the HIIT condition and 13 individuals in the MICT condition (two participants did not accrue the minimum of valid wear days and one accelerometer malfunctioned displaying counts >20,000 during wear time). Mean (±SD) daily wear time was 855 (±175) minutes at baseline and 846 (±63) minutes at follow-up. Eighty-six percent and 98% of participants provided at least 5 valid wear days at baseline and one-month follow-up, respectively.

Manipulation Check.

Accelerometer data collected during the intervention revealed that the accelerometers were able to clearly detect intermittent patterns of HIIT in comparison to the continuous moderate activity characteristic of MICT (see Figures 2(a) and 2(b)). Visual inspection of the accelerometer data (days 7 and 9) and confirmation of exercise heart rate data (days 4, 7, and 9) revealed that all participants were working at the prescribed exercise intensity during the unsupervised training days.

Self-Report Physical Activity Behaviour.

To examine differences in percentage of overall adherence to the exercise prescription over one-month follow-up, an independenttest was conducted. Results revealed a significant difference in adherence rates between HIIT and MICT, (18.96) = 2.08, = 0.05, Cohen's = 0.75. Specifically, individuals in the HIIT condition (89 ± 11%) adhered to their prescribed protocol, to a greater extent than individuals in the MICT condition (71 ± 31%). The same analysis revealed a significant difference in average ratings of perceived exertion between the two conditions, (23) = 2.80, = 0.01, Cohen's = 1.19. As expected, HIIT was perceived to be of greater intensity than MICT (HIIT = 7.4 ± 1.7, MICT = 5.4 ± 1.8).  Table 2. There was, however, a significant difference between the average number of minutes spent in vigorous physical activity per week between the two conditions, (1, 20) = 4.41, = 0.049, Cohen's = 0.92, with HIIT being greater than MICT.

Objective Physical Activity

Changes in Fitness Parameters. Changes in fitness

and anthropometric measures from baseline to one-month follow-up for HIIT and MICT are shown in Table 3    fitness assessed at one-month follow-up. There were no main effects for group or group by time interactions for these fitness parameter variables, indicating that there were no differences in the degree of change experienced between HIIT and MICT over time.

Maximal heart rate achieved at the end of the graded exercise test, body mass, and waist circumference did not change significantly from baseline to one-month followup in either HIIT or MICT ( 's > 0.05). There was a significant main effect of time for systolic blood pressure, (1, 24) = 17.36, < 0.001, Cohen's = 1.75, such that it decreased at one-month follow-up for both conditions. Diastolic blood pressure tended to be lower at one-month follow-up; however, this main effect for time did not reach statistical significance ( = 0.11, Cohen's = 0.13).

Discussion

Physical activity is key in the prevention of T2D and cardiovascular disease in individuals with prediabetes; yet exercise adherence is low in this population [36]. HIIT has recently been touted as an effective and time-efficient exercise option for improving cardiometabolic health [18,37]. However, adherence to HIIT outside of a supervised labbased intervention has not been tested. The present study demonstrates that individuals with prediabetes can adhere to HIIT independently for one month following a very brief supervised laboratory intervention. Interestingly, adherence to HIIT, assessed by self-report in free-living conditions, was greater than standard care exercise involving MICT. In addition, only those individuals randomized to HIIT  (17) 166 (15) 161 (18) 165 (12) 163 (17) 165 (13) 0.14 * value reflects main effect of time from pre to 1 month as per the repeated measures ANOVA.

increased their vigorous physical activity (>6 METS) from baseline to one-month after intervention. Current physical activity guidelines recognize that vigorous physical activity can elicit health benefits in less time when compared to moderate-intensity physical activity. Indeed, guidelines imply that 75 minutes of vigorous activity is equivalent to 150 minutes of moderate activity [38]. However, it is generally assumed that adherence to vigorous exercise will be lower than moderate exercise. This appears based on studies examining the affective response to acute bouts of exercise at different intensities [39]. Our findings provide initial evidence that short-term adherence to vigorous exercise performed as HIIT may be superior to traditional moderate-intensity continuous exercise.

In addition to time-efficiency, vigorous exercise may elicit benefits over and above those accrued through moderateintensity activity. Specifically, NHANES data suggests that individuals accumulating more vigorous-intensity physical activity have reduced odds of metabolic syndrome (closely related to prediabetes), independent of total physical activity levels [19]. Further, when matched for energy expenditure, vigorous physical activity had a greater influence on metabolic syndrome than did moderate intensity physical activity. In other words, it appears that vigorous-intensity physical activity has an important independent role in the prevention of cardiometabolic disease. By design, only those randomized to HIIT in this feasibility study would be expected to increase their minutes of vigorous-intensity physical activity. Indeed, those randomized to HIIT increased their vigorous-intensity physical activity by ∼12 minutes per week while individuals randomized to MICT in this study experienced no increase.

There were no significant differences between conditions in minutes spent in moderate-intensity physical activity or MVPA10+ assessed at one-month follow-up. This was despite individuals in MICT being prescribed 150 minutes of moderate-intensity physical activity per week as compared to individuals in HIIT being prescribed 75 minutes of intermittent vigorous-intensity physical activity. This suggests that objectively measured moderate and total physical activity increased to a similar extent in both groups despite those in the HIIT group being prescribed only ∼50% the amount of time to exercise as those in MICT. Taken together, individuals in HIIT effectively increased time spent in vigorous-intensity physical activity and also saw increases in their moderateintensity physical activity that were comparable to individuals in MICT.

Assessing levels of physical activity objectively by accelerometer following supervised training interventions remains largely unexplored. Our findings indicate that physical activity levels can be increased for up to one month following a brief (10-day) exercise intervention as measured by accelerometry. Specifically, time spent in MVPA10+ was increased following both HIIT and MICT. This was further confirmed with the training logbook data collected in our sample, with >70% adherence measured in both groups. Both HIIT and MICT increased VO 2peak assessed at one-month follow-up, indicating an improvement in fitness. This is promising considering all participants were training under their own volition for one month. A recent meta-analyses reported that the increase in VO 2peak following 12-16 weeks of supervised HIIT is approximately double the increase seen following MICT [17]. Thus, the increase in adherence and vigorous physical activity in the HIIT group may, if adhered to for longer periods of time, lead to greater reductions in cardiometabolic risk when compared to MICT.

The present feasibility study is the first of its kind to assess adherence to HIIT following a supervised laboratory intervention. Such research is needed to determine whether HIIT is a viable health-enhancing exercise strategy in the real world. However, our study is not without limitations. First, we examined independent exercise over a short time period. The results are promising but certainly more research is needed to determine whether individuals with prediabetes can adhere 8 Journal of Diabetes Research to HIIT over the long term. Second, our sample size was small and larger studies are warranted to confirm and expand our preliminary findings. Loss to follow-up was similar in HIIT (2 participants) versus MICT (1 participant), although we were limited by the fact that a further 3 participants in the HIIT group did not complete one-month follow-up testing due to factors unrelated to the study protocol. There are natural safety concerns when implementing vigorous exercise. All participants in our study completed two weeks of supervised HIIT without any reported complications but our study was not designed to examine safety and musculoskeletal injuries in response to HIIT compared to traditional MICT. The small sample size of the current investigation does not permit an accurate assessment of the safety or injury risk potential of HIIT or MICT.

Conclusion

Adherence to exercise in individuals at risk for T2D is remarkably low. HIIT has recently gained popularity as a potential health-enhancing exercise strategy that is timeefficient and distinct from traditional MICT [17,18]. However, the application of HIIT for persons at risk of chronic disease has been questioned due to perceptions that adherence to vigorous-intensity physical activity is unlikely. In this feasibility study, we provide preliminary evidence that individuals with prediabetes can adhere to HIIT over the short term and do so at a level that is greater than MICT. These findings support the potential utility of HIIT as an alternative exercise strategy that could bolster exercise adherence. Future studies are warranted to assess long-term adherence, cardiometabolic benefits, and safety of HIIT in individuals with prediabetes.

Figure 1 :
1Flow of participants through the intervention.

Figure 2 :
2(a) Representative accelerometer counts recorded throughout a bout of HIIT during the intervention. Note: nine intervals were completed in this training session. (b) Representative accelerometer counts recorded throughout a bout of MICT during the intervention. Note: approximately 45 minutes of MICT was completed in this training session.

Behaviour. A series of ANCOVA revealed no significant differences between the HIIT and MICT conditions in the average number of minutes spent in (a) purposeful bouts of MVPA per week (i.e., MVPA10+), (b) overall MVPA per week, and (c) moderate activity per week ( 's > 0.05). Means and standard deviations for each condition are displayed in

. Repeated measures ANOVA revealed a significant main effect of time for absolute VO 2peak , (1, 24) = 20.96, < 0.001, Cohen's = 1.92; relative VO 2peak , (1, 24) = 14.82, < 0.001, Cohen's = 1.62; and peak power output, (1, 24) = 14.08, < 0.001, Cohen's = 1.57, indicating an increase in cardiorespiratory

2 :*
2Mean values for physical activity behaviour before the intervention (pre) and at one-month follow-up (post) for HIIT and MICT, as measured by accelerometers. Difference between HIIT and MICT, < 0.05. a Main effect of time, < 0.05.

Table 1 :
1Baseline characteristics of study participants randomized to high-intensity interval training (HIIT, n = 15) and moderate-intensity continuous exercise (MICT, n = 17) and comparisons between conditions.Variables
All ( = 32)
H I T (= 15)
M I C T (= 17)
Age (years)
51 (10)
5 1 ( 11)
5 1 ( 10)
0.972
Gender, (%)
Male
5 (16.6%)
4 (27.7%)
1 (5.8%)
Female
27 (84.4%)
11 (73.3%)
16 (94.1%)
Body mass (kg)
89.9 (18.8)
89.8 (23)
90 (15)
0.985
Body mass index (kg/m 2 )
32.9 (6.3)
33.1 (7.7)
32.8 (5)
0.904
Waist circumference (cm)
107.3 (14.2)
105.2 (16.5)
109.3 (12.1)
0.426
VO 2 absolute (L/min)
1.81 (0.44)
1.76 (0.38)
1.85 (0.49)
0.551
VO 2 relative (mL/kg/min)
20.23 (4.48)
19.99 (3.58)
20.44 (5.25)
0.783
CANRISK
32 (11)
29 (10)
34 (11)
0.121
HbA1c (%)
5.7 (0.53)
6.1 (0.60)
5.5 (0.36)
0.077
Ethnic origin, (%)
Caucasian
30 (93.8%)
14 (93.3%)
16 (94.1%)
Latin American
1 (3.1%)
0
1 (5.9%)
European
1 (3.1%)
1 (6.7%)
0
Annual income, (%)
$0-$24,999
4 (12.5%)
0
4 (23.5%)
$25,000-$49,999
6 (18.8%)
3 (20.0%)
3 (17.6%)
$50,000-$74,999
10 (31.3%)
5 (33.3%)
5 (29.4%)
$75,000-$99,999
7 (21.9%)
3 (20.0%)
4 (23.5%)
$100,000+
5 (15.7%)
4 (26.7%)
1 (5.9%)

All values are mean (SD) unless indicated as n (%).

Table

Table 3 :
3Changes in fitness and cardiometabolic parameters (mean [SD]) before and 1 month following intervention for study participants randomized to high-intensity interval training (HIIT, = 10) and moderate-intensity continuous exercise (MICT, = 16) and overall ( = 26) effect of time. The current results represent per-protocol analysis.HIIT
MICT
All

 *

Pre
1 month
Pre
1 month
Pre
1 month
Body mass (Kg)
79.0 (17.2)
79.3 (16.4)
88.2 (13.4)
89.3 (12.6)
84.9 (15.3)
85.5 (14.8)
0.70
BMI
29.8 (5.5)
29.9 (5.1)
32.1 (4.1)
31.9 (3.7)
31.2 (4.7)
31.2 (4.3)
0.81
Waist circumference (cm)
97.5 (12.4)
97.5 (13)
108.1 (11.5)
107.4 (10.2)
104.1 (12.8)
103.6 (12.1)
0.65
Blood pressure (mmHg)
Systolic
133 (21)
1 2 5( 15)
1 3 1( 8)
1 2 4( 7)
1 3 2( 14)
1 2 4( 10)
<0.001
Diastolic
82 (7)
7 9( 8)
8 3( 8)
8 1( 8)
8 2( 8)
8 1( 8)
0.11
Absolute VO 2peak (L/min)
1.64 (0.38)
1.79 (0.49)
1.86 (0.51)
1.96 (0.48)
1.77 (0.47)
1.89 (0.48)
<0.001

Relative VO 2peak (mL/kg/min) 20.71 (3.25)
22.63 (4.07)
20.79 (5.21)
21.98 (4.55)
20.76 (4.48)
22.23 (4.30)
<0.001

peak (Watts)
144 (30)
153 (35)
156 (39)
163 (40)
152 (36)
159 (35)
<0.001

Power (Watt/kg)
1.74 (0.47)
1.95 (0.37)
1.76 (0.40)
1.84 (0.35)
1.75 (0.42)
1.88 (0.35)
0.02

peak (BPM)
165
AcknowledgmentsThe authors would like to acknowledge Peter Baumeister, Katelyn Marseden, and Lauren Rex for assistance with VO 2peak testing. This study was supported, in part, by a University of British Columbia Faculty of Health and Social Development Research Grant awarded to Jonathan P. Little and Mary E. Jung.Conflict of InterestsThe authors declare that they have no conflict of interests.
Prediabetes: a high-risk state for diabetes development. A G Tabák, C Herder, W Rathmann, E J Brunner, M Kivimäki, The Lancet. 3799833A. G. Tabák, C. Herder, W. Rathmann, E. J. Brunner, and M. Kivimäki, "Prediabetes: a high-risk state for diabetes develop- ment, " The Lancet, vol. 379, no. 9833, pp. 2279-2290, 2012.

Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. S R Colberg, R J Sigal, B Fernhall, Diabetes Care. 3312S. R. Colberg, R. J. Sigal, B. Fernhall et al., "Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement, " Diabetes Care, vol. 33, no. 12, pp. e147-e167, 2010.

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. W C Knowler, E Barrett-Connor, S E Fowler, The New England Journal of Medicine. 3466W. C. Knowler, E. Barrett-Connor, S. E. Fowler et al., "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin, " The New England Journal of Medicine, vol. 346, no. 6, pp. 393-403, 2002.

Department of Health and Human Services. Physical Activity Guidelines Advisory Committee. U.S; Washington, DC, USAPhysical Activity Guidelines Advisory Committee, Physical Activity Guidelines Advisory Committee Report, U.S. Depart- ment of Health and Human Services, Washington, DC, USA, 2008, http://www.health.gov/paguidelines/report/pdf/ CommitteeReport.pdf.

A Report on Physical Activity for Health from the Four Home Countries' Chief Medical Officers, Department of Health. London, UKDepartment of Health, Start Active, Stay ActiveDepartment of Health, Start Active, Stay Active. A Report on Physical Activity for Health from the Four Home Countries' Chief Medical Officers, Department of Health, London, UK, 2011, https://www.gov.uk/government/publications/start-active- stay-active-a-report-on-physical-activity-from-the-four- home-countries-chief-medical-officers.

. Canadian Society of Exercise Physiology. Canadian Society of Exercise PhysiologyCanadian Society of Exercise Physiology, Canada's Physical Activity Guidelines, Canadian Society of Exercise Physiology, Ottawa, Canada, 2011, http://www.csep.ca/guidelines.

Physical activity in the United States measured by accelerometer. R P Troiano, D Berrigan, K W Dodd, L C Mâsse, T Tilert, M Mcdowell, Medicine and Science in Sports and Exercise. 401R. P. Troiano, D. Berrigan, K. W. Dodd, L. C. Mâsse, T. Tilert, and M. Mcdowell, "Physical activity in the United States measured by accelerometer, " Medicine and Science in Sports and Exercise, vol. 40, no. 1, pp. 181-188, 2008.

Health and Social Care Information Centre, Health Survey for England-2008: Physical Activity and Fitness, The Information Centre. Leeds, UKHealth and Social Care Information Centre, Health Survey for England-2008: Physical Activity and Fitness, The Infor- mation Centre, Leeds, UK, 2009, http://www.hscic.gov.uk/ pubs/hse08physicalactivity.

Physical activity of canadian children and youth: accelerometer results from the 2007 to 2009 canadian health measures survey. R C Colley, D Garriguet, I Janssen, C L Craig, J Clarke, M S Tremblay, Health Reports. 221R. C. Colley, D. Garriguet, I. Janssen, C. L. Craig, J. Clarke, and M. S. Tremblay, "Physical activity of canadian children and youth: accelerometer results from the 2007 to 2009 canadian health measures survey, " Health Reports, vol. 22, no. 1, pp. 15- 23, 2011.

High-intensity interval training to maximize cardiac benefits of exercise training?. U Wisløff, Ø Ellingsen, O J Kemi, Exercise and Sport Sciences Reviews. 373U. Wisløff, Ø. Ellingsen, and O. J. Kemi, "High-intensity interval training to maximize cardiac benefits of exercise training?" Exercise and Sport Sciences Reviews, vol. 37, no. 3, pp. 139-146, 2009.

Aerobic interval training reduces cardiovascular risk factors more than a multitreatment approach in overweight adolescents. A E Tjønna, T O Stølen, A Bye, Clinical Science. 1164A. E. Tjønna, T. O. Stølen, A. Bye et al., "Aerobic interval training reduces cardiovascular risk factors more than a multitreatment approach in overweight adolescents, " Clinical Science, vol. 116, no. 4, pp. 317-326, 2009.

Low-volume highintensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. J P Little, J B Gillen, M E , Journal of Applied Physiology. 1116J. P. Little, J. B. Gillen, M. E. Percival et al., "Low-volume high- intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes, " Journal of Applied Physiology, vol. 111, no. 6, pp. 1554-1560, 2011.

Effects of high-intensity interval exercise versus continuous moderate-intensity exercise on postprandial glycemic control assessed by continuous glucose monitoring in obese adults. J P Little, M E Jung, A E Wright, W Wright, R J F Manders, Nutrition, and Metabolism. 397Applied PhysiologyJ. P. Little, M. E. Jung, A. E. Wright, W. Wright, and R. J. F. Manders, "Effects of high-intensity interval exercise versus con- tinuous moderate-intensity exercise on postprandial glycemic control assessed by continuous glucose monitoring in obese adults, " Applied Physiology, Nutrition, and Metabolism, vol. 39, no. 7, pp. 835-841, 2014.

Exercise snacks' before meals: a novel strategy to improve glycaemic control in individuals with insulin resistance. M E Francois, J C Baldi, P J Manning, Diabetologia. 577M. E. Francois, J. C. Baldi, P. J. Manning et al., "Exercise snacks' before meals: a novel strategy to improve glycaemic control in individuals with insulin resistance, " Diabetologia, vol. 57, no. 7, pp. 1437-1445, 2014.

Acute high-intensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycaemia in patients with type 2 diabetes. J B Gillen, J P Little, Z Punthakee, M A Tarnopolsky, M C Riddell, M J Gibala, Diabetes, Obesity and Metabolism. 146J. B. Gillen, J. P. Little, Z. Punthakee, M. A. Tarnopolsky, M. C. Riddell, and M. J. Gibala, "Acute high-intensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycaemia in patients with type 2 diabetes, " Diabetes, Obesity and Metabolism, vol. 14, no. 6, pp. 575-577, 2012.

The potential for high-intensity interval training to reduce cardiometabolic disease risk. H S Kessler, S B Sisson, K R Short, Sports Medicine. 426H. S. Kessler, S. B. Sisson, and K. R. Short, "The potential for high-intensity interval training to reduce cardiometabolic disease risk, " Sports Medicine, vol. 42, no. 6, pp. 489-509, 2012.

High-intensity interval training in patients with lifestyle-induced cardiometabolic Journal of Diabetes Research 9 disease: a systematic review and meta-analysis. K S Weston, U Wisløff, J Coombes, British Journal of Sports Medicine. 48K. S. Weston, U. Wisløff, and J. Coombes, "High-intensity inter- val training in patients with lifestyle-induced cardiometabolic Journal of Diabetes Research 9 disease: a systematic review and meta-analysis, " British Journal of Sports Medicine, vol. 48, pp. 1227-1234, 2014.

Physiological adaptations to low-volume, high-intensity interval training in health and disease. M J Gibala, J P Little, M J Macdonald, J A Hawley, The Journal of Physiology. 5905M. J. Gibala, J. P. Little, M. J. Macdonald, and J. A. Hawley, "Physiological adaptations to low-volume, high-intensity inter- val training in health and disease, " The Journal of Physiology, vol. 590, no. 5, pp. 1077-1084, 2012.

Vigorous intensity physical activity is related to the metabolic syndrome independent of the physical activity dose. I Janssen, R Ross, ID dys038International Journal of Epidemiology. 414I. Janssen and R. Ross, "Vigorous intensity physical activity is related to the metabolic syndrome independent of the physical activity dose, " International Journal of Epidemiology, vol. 41, no. 4, Article ID dys038, pp. 1132-1140, 2012.

Correlates of adults' participation in physical activity: review and update. S G Trost, N Owen, A E Bauman, J F Sallis, W Brown, Medicine and Science in Sports and Exercise. 3412S. G. Trost, N. Owen, A. E. Bauman, J. F. Sallis, and W. Brown, "Correlates of adults' participation in physical activity: review and update, " Medicine and Science in Sports and Exercise, vol. 34, no. 12, pp. 1996-2001, 2002.

The pleasure and displeasure people feel when they exercise at different intensities: decennial update and progress towards a tripartite rationale for exercise intensity prescription. P Ekkekakis, G Parfitt, S J Petruzzello, Sports Medicine. 418P. Ekkekakis, G. Parfitt, and S. J. Petruzzello, "The pleasure and displeasure people feel when they exercise at different intensities: decennial update and progress towards a tripartite rationale for exercise intensity prescription, " Sports Medicine, vol. 41, no. 8, pp. 641-671, 2011.

ACSM's Guidelines for Exercise Testing and Prescription. Lippincott Williams & WilkinsPhiladelphia, Pa, USA9th editionAmerican College of Sports Medicine, ACSM's Guidelines for Exercise Testing and Prescription, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 9th edition, 2010.

Where does HIT fit? An examination of the affective response to highintensity intervals in comparison to continous moderate-and continuous vigorous-intensity exercise in the exercise intensityaffect continuum. M E Jung, J E Bourne, J P Little, R L Newton, ID e114541PLoS ONE. 912M. E. Jung, J. E. Bourne, J. P. Little, and R. L. Newton, "Where does HIT fit? An examination of the affective response to high- intensity intervals in comparison to continous moderate-and continuous vigorous-intensity exercise in the exercise intensity- affect continuum, " PLoS ONE, vol. 9, no. 12, Article ID e114541, 2014.

Diagnosis and classification of diabetes mellitus. Diabetes Care. 351American Diabetes AssociationAmerican Diabetes Association, "Diagnosis and classification of diabetes mellitus, " Diabetes Care, vol. 35, supplement 1, pp. S64-S71, 2012.

CANRISK: The Canadian Diabetes Risk Questionnaire User Guide for Pharmacists, Public Health Agency of Canada. Ottawa, CanadaPublic Health Agency of CanadaPublic Health Agency of Canada, CANRISK: The Canadian Diabetes Risk Questionnaire User Guide for Pharmacists, Public Health Agency of Canada, Ottawa, Canada, 2011, http:// www.healthycanadians.gc.ca/health-sante/disease-maladie/di- abetes-diabete/canrisk/index-eng.php.

The physical activity readiness questionnaire (PAR-Q+) and electronic physical activity readiness medication examination (ePARmed-X+). D E R Warburton, V K Jamnik, S S D Bredin, N Gledhill, Health & Fitness Journal of Canada. 42D. E. R. Warburton, V. K. Jamnik, S. S. D. Bredin, and N. Gled- hill, "The physical activity readiness questionnaire (PAR-Q+) and electronic physical activity readiness medication examina- tion (ePARmed-X+), " Health & Fitness Journal of Canada, vol. 4, no. 2, pp. 3-23, 2011.

Social Foundations of Thought and Action: A Social Cognitive Theory. A Bandura, Prentice HallEnglewood Cliffs, NJ, USAA. Bandura, Social Foundations of Thought and Action: A Social Cognitive Theory, Prentice Hall, Englewood Cliffs, NJ, USA, 1986.

Borg's Perceived Exertion and Pain Scales. G Borg, Human Kinetics. G. Borg, Borg's Perceived Exertion and Pain Scales, Human Kinetics, Champaign, Ill, USA, 1998.

Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years. A C King, W L Haskell, D R Young, R K Oka, M L Stefanick, Circulation. 9110A. C. King, W. L. Haskell, D. R. Young, R. K. Oka, and M. L. Ste- fanick, "Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years, " Circulation, vol. 91, no. 10, pp. 2596-2604, 1995.

Validation of accelerometer wear and nonwear time classification algorithm. L Choi, Z Liu, C E Matthews, M S Buchowski, Medicine & Science in Sports & Exercise. 432L. Choi, Z. Liu, C. E. Matthews, and M. S. Buchowski, "Vali- dation of accelerometer wear and nonwear time classification algorithm, " Medicine & Science in Sports & Exercise, vol. 43, no. 2, pp. 357-364, 2011.

Calibration of the computer science and applications, Inc. accelerometer. P S Freedson, E Melanson, J Sirard, Medicine & Science in Sports & Exercise. 305P. S. Freedson, E. Melanson, and J. Sirard, "Calibration of the computer science and applications, Inc. accelerometer, " Medicine & Science in Sports & Exercise, vol. 30, no. 5, pp. 777- 781, 1998.

Sustained and shorter bouts of physical activity are related to cardiovascular health. N L Glazer, A Lyass, D W Esliger, Medicine and Science in Sports and Exercise. 451N. L. Glazer, A. Lyass, D. W. Esliger et al., "Sustained and shorter bouts of physical activity are related to cardiovascular health, " Medicine and Science in Sports and Exercise, vol. 45, no. 1, pp. 109-115, 2013.

How many days of monitoring predict physical activity and sedentary behaviour in older adults?. T L Hart, A M Swartz, S E Cashin, S J Strath, International Journal of Behavioral Nutrition and Physical Activity. 862T. L. Hart, A. M. Swartz, S. E. Cashin, and S. J. Strath, "How many days of monitoring predict physical activity and sedentary behaviour in older adults?" International Journal of Behavioral Nutrition and Physical Activity, vol. 8, article 62, 2011.

Insulin resistance, metabolic syndrome, and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA). A G Bertoni, N D Wong, S Shea, Diabetes Care. 3011A. G. Bertoni, N. D. Wong, S. Shea et al., "Insulin resistance, metabolic syndrome, and subclinical atherosclerosis: the Multi- Ethnic Study of Atherosclerosis (MESA), " Diabetes Care, vol. 30, no. 11, pp. 2951-2956, 2007.

The 2014 Canadian Hypertension Education Program Recommendations, Canadian Hypertension Education Program. Canadian Hypertension Education Program. Canadian Hypertension Education Program, The 2014 Cana- dian Hypertension Education Program Recommendations, Cana- dian Hypertension Education Program, Ontario, Canada, 2014, http://www.hypertension.ca/images/CHEP 2014/.

Patients with diabetes in cardiac rehabilitation: attendance and exercise capacity. M J Armstrong, B.-J Martin, R Arena, Medicine and Science in Sports and Exercise. 465M. J. Armstrong, B.-J. Martin, R. Arena et al., "Patients with diabetes in cardiac rehabilitation: attendance and exercise capacity, " Medicine and Science in Sports and Exercise, vol. 46, no. 5, pp. 845-850, 2014.

The role of exercise interval training in treating cardiovascular disease risk factors. C Earnest, Current Cardiovascular Risk Reports. 34C. Earnest, "The role of exercise interval training in treating cardiovascular disease risk factors, " Current Cardiovascular Risk Reports, vol. 3, no. 4, pp. 296-301, 2009.

Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. C E Garber, B Blissmer, M R Deschenes, Medicine and Science in Sports and Exercise. 437C. E. Garber, B. Blissmer, M. R. Deschenes et al., "Quantity and quality of exercise for developing and maintaining cardiorespi- ratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise, " Medicine and Science in Sports and Exercise, vol. 43, no. 7, pp. 1334-1359, 2011.

Vigorous exercise in clinical practice: balancing risks and benefits. M F F Mediano, V L M Pinto, F D S N S Mendes, G M S Silva, A S Sousa, Medicine & Science in Sports & Exercise. 4651053M. F. F. Mediano, V. L. M. Pinto, F. D. S. N. S. Mendes, G. M. S. Silva, and A. S. Sousa, "Vigorous exercise in clinical practice: balancing risks and benefits, " Medicine & Science in Sports & Exercise, vol. 46, no. 5, p. 1053, 2014.


Impact of surgical management in cases of intraoperative membrane perforation during a sinus lift procedure: a follow-up on bone graft stability and implant success

Benedicta E Beck-Broichsitter
Dorothea Westhoff
Eleonore Behrens
Jörg Wiltfang
Stephan T Becker
Impact of surgical management in cases of intraoperative membrane perforation during a sinus lift procedure: a follow-up on bone graft stability and implant success
10.1186/s40729-018-0116-8R E S E A R C H Open Access
Background: Until now, sinus floor elevation represents the gold standard procedure in the atrophic maxilla in order to facilitate dental implant insertion. Although the procedure remains highly predictive, the perforation of the Schneiderian membrane might compromise the stability of the augmented bone and implant success due to chronic sinus infection. The aim of this retrospective cohort study was to show that a membrane tear, if detected and surgically properly addressed, has no influence on the survival of dental implants and bone resorption in the augmented area. Methods: Thirty-one patients with 39 perforations could be included in this evaluation, and a control group of 32 patients with 40 sinus lift procedures without complications were compared regarding the radiographically determined development of bone level, peri-implant infection, and implant loss. Results: Implant survival was 98.9% in the perforation group over an observation period of 2.7 (± 2.03) years compared to 100% in the control group after 1.8 (± 1.57) years. The residual bone level was significantly lower in the perforation group (p = 0.05) but showed no difference direct postoperatively (p = 0.7851) or in the follow-up assessment (p = 0.2338). Bone resorption remained not different between both groups (p = 0.945). A two-stage procedure was more frequent in the perforation group (p = 0.0003) as well as peri-implantitis (p = 0.0004). Conclusions: Within the limits of our study, the perforation of the Schneiderian membrane did not have a negative impact on long-term graft stability or the overall implant survival.

Background

Sinus floor elevation procedures have become a predictable and successful treatment, performed when the maxillary alveolar ridge is atrophied and the bone height is not sufficient for primary implantation. If the postoperative course remains uneventful, the outcome is highly predictable [1][2][3]. However, complications may have a negative impact on the overall treatment success. As a common complication, perforation of the Schneiderian membrane occurs in 12 to 44% of cases depending on the literature [2,[4][5][6], with an average of 20 to 25% [7][8][9] in all cases due to septa morphological aspects of the membrane or other pathologic conditions; the perforation itself represents the major intraoperative complication despite common complications, such as postoperative infection [5,10].

Still, it is not completely clear to what extent these complications influence implant survival or might impact the augmented material in the sinus. To evaluate the impact of early-onset complications during implant insertion on the implant success, Becker et al. published a follow-up study evaluating the first year after a sinus lift procedure [11], which did not reveal a negative impact on implant survival after an observation period of 162 days. In contrast to these results, a study by Nolan et al. retrospectively re-assessed a total of 359 sinus augmentation procedures with a perforation rate of 41.8% (150 patients) at least 1 year after implant loading and reported a graft failure rate of 6.7%, in which 70.8% of membranes were perforated. In a study by Sakkas et al. [12], membrane tear (perforation rate 10.8%) was slightly not significantly associated with postoperative complications in 105 sinus lift procedures. A highly significant connection was shown in a study by Schwartz-Arad et al. [5], but these complications reportedly had no impact on implant survival.

In this retrospective study, the patient cohort with perforations of the Schneiderian membrane from the previously reported study [11] was re-evaluated to specifically assess local bone remodeling and resorption processes in the augmented area, signs of chronic infection of the sinus, and implant survival compared to a group of patients without a membrane tear over a longer time period. We hypothesize that if detected and properly handled surgically or with an adequate adaption of the surgical protocol, a perforation of the Schneiderian membrane would not endanger the outcome parameters of stable bone augmentation and promotion of signs of periimplant disease and implant loss.

Methods

Patient recruitment

In accordance with the WMA Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects, approval was given by the local ethics committee of the Christian-Albrechts-University in Kiel (AZ 132/10). All patients gave informed written consent to participate.

A total of 201 sinus floor elevation procedures, which were performed from 2005 to 2006 in the Department of Oral and Maxillofacial Surgery of the University Hospital of Kiel, were primarily included in this retrospective cohort study. Within this cohort, 41 perforations (20.4%) of the Schneiderian membrane in 33 patients (21 female, 12 male) occurred. One patient was deceased, and one patient did not engage in the followup offered by the department. After exclusion of these two patients, a total of 31 patients aged 60.86 (± 11.21) years with 39 perforations were available to participate in regular recall examinations with an average observation time of 2.69 years (± 2.04 years). According to this study group, 32 patients with 40 sinus lift procedures without perforations aged 58.76 years (± 9.43) were randomized from the cohort to represent the control group (average observation time 2.14 years ± 1.85 years). Patients were recruited from the established recall system in the department. Requirements of inclusion were engagement in at least three follow-up visits after dental implantation and receiving dental implants in the department, if a twostage procedure was performed. The inclusion rate of patients in the control group was 33.28%. In total, 56.16% of patients (54 patients) within the control group had not completed the follow-up visits for various reasons (relocation, impairment because of age, follow-up performed elsewhere) and therefore were excluded. Sixteen patients received implants in other private practices (16.64%), and 2 patients were deceased.

Medical record assessment

The manufacturer and position of implants were previously extracted from surgical reports in the medical record, as were in-house treated implant failures and consecutive explanation procedures. Vertical bone augmentation was additionally classified dependent on donor site (none/linea obliqua/iliac crest/scapula).

Implant therapy

Three different oral and maxillofacial surgeons performed the sinus lift procedure with an external approach according to comparable surgical standards and inserted all implants examined in this study in a submerged protocol with uncovering after 3-4 months due to the manufacturer's surgical recommendations. Specifically, a total of 35 external sinus floor elevations were performed through a bone window in the facial aspect of the maxillary sinus. The internal sinus lift approach was applied once. In four patients, sinus floor elevation was accompanied with a LeFort I osteotomy or in one case with a reconstruction of the maxilla after tumor surgery. Preexisting defects were assumed due to trauma or previous surgical interventions in three operation sites.

For sinus floor augmentation including defects of less than 2 cm 3 , bone filter material and bone substitute [13,14] were applied. If the defect exceeded 2 cm 3 , only autologous bone was used.

Perforations up to a diameter of 5 mm in size were covered with a BioGide membrane (Geistlich, Wolhusen, Switzerland), and perforations beyond a diameter of 5 mm up to 10 mm were additionally stitched with resorbable sutures (Vicryl 6-0, Ethicon, Norderstedt, Germany) while larger defects led to termination of the procedure. Only in exceptional cases were perforations left untreated or sealed with fibrin glue.

Implants were either placed in a one-stage procedure accompanied with the sinus floor elevation or in a twostage procedure if primary stability might not be achieved due to the bone being present.

Patients received antibacterial mouth rinse, systemic antibiotics, nose drops, and inhalants from 7 to 10 days beginning directly after the operation. Sutures were removed 7 to 10 days after the surgical procedure. All patients were instructed how to maintain appropriate oral hygiene directly after surgical intervention and were re-instructed after the uncovering procedure and during recall sessions. Patients were further asked to join for regular recall examinations after prosthodontic rehabilitation and thereafter each year. Six months after sinus floor elevation, panoramic radiographs were made.

Clinical assessment

One independent oral and maxillofacial surgeon performed the clinical follow-up examinations according to a standardized protocol. A peri-implant probing including probing pocket depths and recessions on four sites of each implant was assessed as was bleeding on probing (BOP) to determine the status of oral hygiene objectively. Signs of gingivitis and pus suppuration were also recorded. The criteria of peri-implantitis were based on those published by Ong et al. [15]: peri-implant probing depth ≥ 5 mm and bleeding on probing and/or suppuration and radiographic bone loss ≥ 2.5 mm.

Based on panoramic radiographs, marginal bone levels were measured on the distal and mesial sites of each implant. Bone loss was calculated based on the known implant length and the radiographic magnification factors accordingly. Distances were measured to the nearest millimeter. Bone levels after sinus floor elevation were compared to bone levels in follow-up ( Fig. 1).

The implant success rate was defined as the absence of patients' complaints and objective signs of peri-implant inflammation (bleeding on probing, periimplantitis, dehiscence defects, and implant stability).

Statistical assessment

Statistical data analyses were performed using GraphPad Prism version 6.0 (GraphPad Software, La Jolla, CA, USA). Descriptive statistics (mean value, standard deviation, and percentage distribution) were calculated, and the data were checked for Gaussian distribution applying the Shapiro-Wilk test. Comparisons between the groups with and without perforation were assessed with non-parametric statistic testing (Mann-Whitney-U-Wilcoxon). Fisher's exact test was applied for combinations of factors, and implant survival was displayed in a Kaplan-Meier plot. Multiple comparisons according to Tukey were applied in cases of further subdivision of the  datasets. If the probability of error was less than 5%, the result was presented as statistically significant.

Results

Descriptive statistical evaluation Perforation group

The mean control interval was 2.69 (± 2.03) years. At the time of the follow-up examination, the average age was 59.95 (± 11.82) years.

In the remaining collective of 31 patients (96.97%; 12 males (37.54%) and 19 females (59.43%)), a total of 92 implants were inserted. The overview of perforation treatment in the study group is given in Fig. 2, and Fig. 3 depicts the reasons for perforations. Eleven implants (11.96%) were inserted in a one-stage procedure, whereas the remaining 81 implants (88.04%) were inserted in a second surgical intervention. One implant (1.09%) had to be removed due to wound infection 3 months after implant insertion. After a 6month healing period, the implant could be successfully replaced.

Many implants were purchased from Nobel Biocare with a total of 33 (35.87%), followed by Camlog with 24 (26.09%), Straumann with 18 (19.57%), Ankylos with 10 (10.87%), and Frialit with 5 implants (5.43%). The Astra implant system was applied twice (2.17%).

Twelve implants showed a probing depth above 3 mm; bleeding on probing was positive in 7 implants, and 6 implants showed signs of peri-implantitis or patients had previously had peri-implant surgery.

Control group

The patients' (16 female, 15 male) mean age included in this group was 59.32 years (± 11.34 years) with a mean observation period of 1.80 years (± 1.57 years).

A total of 83 implants were inserted, of which 30 implants were inserted in a one-stage procedure and 53 in a two-stage procedure. No implant had to be removed during the observation period.

Forty-two implants were purchased from Camlog (50.6%), followed by Nobel Biocare with 22 implants (26.51%), Straumann with 18 implants (21.69%), and one Astra implant (1.2%). No signs of inflammation or periimplantitis were detected in the clinical examinations.

Group comparison

The preferred implant positions in both groups are depicted in Table 1, showing a homogenous distribution when comparing both groups. Table 2 provides an overview of bone graft origin. In the control group, the majority of procedures (65.1%) did not require an additional bone graft, whereas 59.8% of surgical interventions required iliac crest in the perforation group.

The initial bone level differed significantly (p = 0.05) between both groups with a median value of 5.69 mm in the study group and 3.87 mm in the control group (Fig. 4). A Mann-Whitney-U-Wilcoxon test revealed no significant difference between bone level postoperatively (p = 0.7851; median value control group 17.40 mm; median value perforation group 16.91 mm), in follow-up (p = 0.2238; median value control group 13.88 mm; median value perforation group 13.31 mm), or for bone resorption (p = 0.9455, median value study/perforation group 3.45 mm; Fig. 5). The data are further summarized in Table 3.

Groups were further subdivided and separated at an initial bone level of 4 mm, above which the sinus lift procedure is considered a relative indication for achievement of primary stability [16]. Regarding the height of augmented sinus floor postoperatively, a multiple comparison analysis revealed a significant difference between the groups. The adjusted p values of multiple comparisons are depicted in Table 4. Interestingly, only two group comparisons revealed a relevant difference. Multiple comparisons of bone resorption in subgroups did not reveal a statistically significant difference (p = 0.1418).

Fisher's exact test revealed a statistically significant difference of proportions of one-stage versus two-stage procedures due to the presence of perforation (p = 0.0003; Table 5) and a significantly higher trend for peri-implantitis in patients with perforation (p = 0.0004; Table 6).

Discussion

The aim of this retrospective cohort study was to evaluate the impact of intraoperative perforations of the Schneiderian membrane during sinus floor elevation on the stability of the augmented area and its influence on osseointegration after implant insertion. Therefore, we could re-assess a patient cohort of originally 34 patients with 41 perforations and compare their outcome with a control group of patients with sinus floor elevation but without membrane tear, offering a long-term perspective over a range of 1.8 years in the control group to 2.7 years in the study group.

Although the height of the alveolar crest differed significantly, the total postoperative height of augmented and residual bone was on a comparable level allowing for sufficient elevation of the sinus floor to insert dental implants independently of a perforation. This fact remains reassuring as the latter represents the mostly common complication with a reported variation of 10 to 44% [5,6,8,12,[17][18][19][20][21][22][23].

In this context, the surgical experience and the tissue quality, e.g., scarring due to previous procedures or local inflammation, might lead to a high probability of Schneiderian membrane perforation [16,22,24,25] with anatomical variations, such as sinus septa or thin, vulnerable membrane textures [4,16,22,24,25]. Some studies have suggested contraindication of sinus floor elevation in patients with anatomical variations such as septa or mucosal swelling [8]. As our results did not indicate any negative impact of membrane tear on the augmented sinus, the results of Nolan et al., including a total of 359 sinus floor augmentations, indicated that graft failure occurred in 6.7% of all procedures and was significantly correlated (p = 0.0028) with membrane perforation. Compared to our evaluation, where procedures were, without exception, performed by attending physicians, the perforation rate was twice as high (21 vs. 41%). Surgical experience was ruled out as an influencing factor, as membrane perforations were equally distributed in cases treated by attending physicians compared to those performed by residents [6]. Another reason for the different findings might be due to the differences between the numbers of compared membrane tears (39 perforations vs. 150 perforations), as both evaluations were performed retrospectively.

One implant was lost in the perforation group due to early-onset peri-implantitis, whereas all implants in the control group were still in place. As we had previously prospectively reported on the first 6 months after dental implantation in this cohort [11], there was no further impact of membrane perforation on implant loss for at least 12 to 24 months in this retrospective evaluation. The appearance of peri-implantitis was more often observed in patients who experienced a procedure with an intraoperative perforation. However, this finding might be because the control group did not fully represent the patients without membrane perforation as only one third engaged in a sufficient followup. The reduced time span of the patients' observation time in the control group might be due to the lack of postoperative complications in this group who did have follow-up examinations in the department. Therefore, we cannot conclude whether there is or is not an impact based on the results in our study cohort. Sakkas et al. reported no impact of membrane perforation on the overall implant within a 1-year evaluation [12], whereas Proussaefs et al. reported a decreased implant survival in two-stage procedures and membrane tear compared  to intact membranes (69.56 vs. 100%) [10], as did a study published by Khoury [7].

In our study, bone resorption in the augmented area did not differ significantly between sinus lifting procedures with or without perforations. It is now widely accepted that following initial bone remodeling after an augmentation procedure followed by a dental implantation, bone loss within the following 3 years with implants in the interproximal space should be less than 0.5 mm in radiographic evaluations [26,27]. Consistent with the results of Sakkas et al., there was no impact of bone graft origin or postoperative complications in patients with perforation of the Schneiderian membrane [12], similar to a study by Moreno Vazquez et al., which also did not find a correlation between complications, graft failure, and membrane perforation, assessing 8 years postoperatively [24]. In contrast to these studies, Proussaefs et al. reported a significant negative impact of membrane tear on bone formation in the sinus, more soft tissue formation, and less contact of graft particles to the residual bone [10].

The surgical management in cases of a membrane perforation might also influence the overall postoperative outcome and complications. Although the sinus lifting procedure has been established for many years now, there are no evidence-based guidelines for perforation closure or indications to interrupt the procedure. To date, most existing studies recommend sealing smaller sizes of perforations with membranes (collagen, demineralized laminar bone) or fibrin glue. Additional resorbable sutures in cases of larger perforations are advisable if a complete closure of the perforation is feasible [5,8,28] but have not been shown to be superior as the coverage of larger perforations with membranes alone were shown to be effective [9,12,28,29]. A lateral approach in sinus lifting might be obligatory to securely detect and therefore treat a perforation. In the primary assessment of the study, four procedures had to be terminated due to an extensive perforation, thin mucosa, or a retention cyst. After waiting 6 months, the procedure was repeated without any complications [11]. Other studies also recommend interrupting the procedure, when the repair does not seem to be sufficiently possible [7,17].

In this study, a one-stage procedure was significantly less likely to result in membrane perforation. Implant insertion was immediately performed only if the estimated residual bone quality ensured high primary stability, which was consistent with a study by Cha et al. [3]. Residual bone height between 1 to 3 mm was not favorable for immediate implant insertion after sinus floor elevation with a lateral approach [16]. Therefore, the surgeon should be aware that a two-stage approach includes the risk of further complications relating to the surgical procedure itself. A recently published study revealed a significantly higher risk for soft-tissue complications in cases of a second procedure [30].

Due to the retrospective nature of this study, the management in cases of perforation did not follow a standardized protocol. Most of the studies regarding the outcome after membrane tear rely on retrospectively acquired data, and similar to in our study, with an inhomogeneous study cohort with different approaches in cases of perforation, there were different augmentation procedures, including grafts and grafting material, oneand two-stage procedures and different types of dental implants. Based on our data and regarding the limitations within the design of this study, we might conclude that a perforation of the Schneiderian membrane, if  recognized and properly addressed, does not necessarily endanger or negatively impact the stability of the augmented bone or implant survival. To systematically assess the impact of membrane perforation on the augmented sinus and implant survival, prospective studies and higher case numbers should be considered in the future.

Conclusions

In conclusion, and within the limits of its retrospective nature, our study implies that in cases of intraoperative perforation of the Schneiderian membrane, a consequent surgical assessment and treatment might avoid complications regarding graft stability and implant survival. Two-stage procedures might be appropriate if primary stability does not seem to be achievable. Augmentation of the sinus floor might be possible even in cases of perforation. A negative impact on the bone graft itself or on remodeling processes in follow-up could not have been shown, but prospective longterm studies should be performed to deliver reliable data on the impact of membrane perforation on graft stability and implant survival.

Funding

This study was not funded.

Authors' contributions BEBB made substantial contributions to the conception and design and analysis and interpretation of data and drafting the manuscript and revising it critically for important intellectual content. BEBB gave final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. DW contributed to the acquisition of data and revising the manuscript critically for important intellectual content. DW gave final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. EB made substantial contributions to the conception and design of the study and revising the manuscript critically for important intellectual content. EB gave final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. JW made substantial contributions to the conception and design and revising the manuscript critically for important intellectual content. JW gave final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. STB made substantial contributions to the conception and design and revising the manuscript critically for important intellectual content. STB gave final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Fig. 1
1Bone levels after sinus floor elevation

Fig. 2
2Overview of the perforation treatment in the study groupFig. 3Reasons for perforations

Fig. 4
4The initial bone level of the control group and the perforation group

Fig. 5
5Bone resorption in the follow-up of the control group and the perforation group

Table 1
1Distribution of implant positionsImplant position
3
4
5
6
7
8

Perforation group
7
7.6%
23
25.0%
27
29.4%
30
32.6%
5
5.4%
0
0%

Control group
9
10.8%
20
24.1%
25
30.1%
21
25.3%
7
8.4%
1
1.2%

Table 2
2Origin of bone graftOrigin of bone graft
No bone graft
Linea obliqua
Iliac crest
Scapula flap

Perforation group
15
16.3%
22
23.9%
55
59.8%
0
0%

Control group
54
65.1%
11
13.3%
13
15.7%
5
6.02%

Table 3
3Data summary of bone level developmentBone level preoperatively
Bone level postoperatively
Bone level follow-up
Bone resorption

Perforation
group

Control
group

Perforation
group

Control
group

Perforation
group

Control
group

Perforation
group

Control
group

Median value
3.87
5.69
16.91
17.40
13.31
13.88
3.45
3.45

Standard deviation
3.79
3.32
5.06
6.04
2.39
4.02
4.84
7.64

p value
0.05
0.7851
0.2235
0.9455

Table 5
5Fisher's exact test: surgical strategy dependent on membrane perforation (p = 0.0003)One-stage procedure
Two-stage procedure

Perforation group
11
81

Control group
30
53

Table 6
6Fisher's exact test: incidence of peri-implant disease after sinus lifting procedure with and without membrane perforation (p = 0.0004)Peri-implantitis
No peri-implantitis

Perforation group
12
80

Control group
0
83

Competing interestsThe authors Benedicta Beck-Broichsitter, Dorothea Westhoff, Eleonore Behrens, Jörg Wiltfang, and Stephan T. Becker declare that there are no existing competing interests concerning this collaborative work.
Onlay augmentation versus sinuslift procedure in the treatment of the severely resorbed maxilla: a 5-year comparative longitudinal study. J Wiltfang, S Schultze-Mosgau, E Nkenke, M Thorwarth, F W Neukam, K A Schlegel, Int J Oral Maxillofac Surg. 348Wiltfang J, Schultze-Mosgau S, Nkenke E, Thorwarth M, Neukam FW, Schlegel KA. Onlay augmentation versus sinuslift procedure in the treatment of the severely resorbed maxilla: a 5-year comparative longitudinal study. Int J Oral Maxillofac Surg. 2005;34(8):885-9.

Maxillary sinus membrane repair: report of a technique for large perforations. M A Pikos, Implant Dent. 81Pikos MA. Maxillary sinus membrane repair: report of a technique for large perforations. Implant Dent. 1999;8(1):29-34.

Simultaneous sinus lift and implant installation: prospective study of consecutive two hundred seventeen sinus lift and four hundred sixty-two implants. H S Cha, A Kim, H Nowzari, H S Chang, K M Ahn, Clin Implant Dent Relat Res. 163Cha HS, Kim A, Nowzari H, Chang HS, Ahn KM. Simultaneous sinus lift and implant installation: prospective study of consecutive two hundred seventeen sinus lift and four hundred sixty-two implants. Clin Implant Dent Relat Res. 2014;16(3):337-47.

Prevalence, location and morphology of maxillary sinus septa: systematic review and meta-analysis. B Pommer, C Ulm, M Lorenzoni, R Palmer, G Watzek, W Zechner, J Clin Periodontol. 398Pommer B, Ulm C, Lorenzoni M, Palmer R, Watzek G, Zechner W. Prevalence, location and morphology of maxillary sinus septa: systematic review and meta-analysis. J Clin Periodontol. 2012;39(8):769-73.

The prevalence of surgical complications of the sinus graft procedure and their impact on implant survival. D Schwartz-Arad, R Herzberg, E Dolev, J Periodontol. 754Schwartz-Arad D, Herzberg R, Dolev E. The prevalence of surgical complications of the sinus graft procedure and their impact on implant survival. J Periodontol. 2004;75(4):511-6.

Correlation between Schneiderian membrane perforation and sinus lift graft outcome: a retrospective evaluation of 359 augmented sinus. P J Nolan, K Freeman, R A Kraut, J Oral Maxillofac Surg. 721Nolan PJ, Freeman K, Kraut RA. Correlation between Schneiderian membrane perforation and sinus lift graft outcome: a retrospective evaluation of 359 augmented sinus. J Oral Maxillofac Surg. 2014;72(1):47-52.

Augmentation of the sinus floor with mandibular bone block and simultaneous implantation: a 6-year clinical investigation. F Khoury, Int J Oral Maxillofac Implants. 144Khoury F. Augmentation of the sinus floor with mandibular bone block and simultaneous implantation: a 6-year clinical investigation. Int J Oral Maxillofac Implants. 1999;14(4):557-64.

Anatomical aspects of sinus floor elevations. J P Van Den Bergh, C M Ten Bruggenkate, F J Disch, D B Tuinzing, Clin Oral Implants Res. 113van den Bergh JP, ten Bruggenkate CM, Disch FJ, Tuinzing DB. Anatomical aspects of sinus floor elevations. Clin Oral Implants Res. 2000;11(3):256-65.

A prospective randomized study of 1-and 2-stage sinus inlay bone grafts: 1-year followup. K Wannfors, B Johansson, M Hallman, T Strandkvist, Int J Oral Maxillofac Implants. 155Wannfors K, Johansson B, Hallman M, Strandkvist T. A prospective randomized study of 1-and 2-stage sinus inlay bone grafts: 1-year follow- up. Int J Oral Maxillofac Implants. 2000;15(5):625-32.

Repair of the perforated sinus membrane with a resorbable collagen membrane: a human study. P Proussaefs, J Lozada, J Kim, M D Rohrer, Int J Oral Maxillofac Implants. 193Proussaefs P, Lozada J, Kim J, Rohrer MD. Repair of the perforated sinus membrane with a resorbable collagen membrane: a human study. Int J Oral Maxillofac Implants. 2004;19(3):413-20.

Prospective observation of 41 perforations of the Schneiderian membrane during sinus floor elevation. S T Becker, H Terheyden, A Steinriede, E Behrens, I Springer, J Wiltfang, Clin Oral Implants Res. 1912Becker ST, Terheyden H, Steinriede A, Behrens E, Springer I, Wiltfang J. Prospective observation of 41 perforations of the Schneiderian membrane during sinus floor elevation. Clin Oral Implants Res. 2008;19(12):1285-9.

Effect of Schneiderian membrane perforation on sinus lift graft outcome using two different donor sites: a retrospective study of 105 maxillary sinus elevation procedures. A Sakkas, I Konstantinidis, K Winter, A Schramm, F Wilde, GMS Interdiscip Plast Reconstr Surg DGPW. 511Sakkas A, Konstantinidis I, Winter K, Schramm A, Wilde F. Effect of Schneiderian membrane perforation on sinus lift graft outcome using two different donor sites: a retrospective study of 105 maxillary sinus elevation procedures. GMS Interdiscip Plast Reconstr Surg DGPW. 2016;5:Doc11.

Particulated bone grafts-effectiveness of bone cell supply. I N Springer, H Terheyden, S Geiss, F Harle, J Hedderich, Y Acil, Clin Oral Implants Res. 152Springer IN, Terheyden H, Geiss S, Harle F, Hedderich J, Acil Y. Particulated bone grafts-effectiveness of bone cell supply. Clin Oral Implants Res. 2004; 15(2):205-12.

Maxillary sinus augmentation: histologic and histomorphometric analysis. A Barone, R Crespi, N N Aldini, M Fini, R Giardino, U Covani, Int J Oral Maxillofac Implants. 204Barone A, Crespi R, Aldini NN, Fini M, Giardino R, Covani U. Maxillary sinus augmentation: histologic and histomorphometric analysis. Int J Oral Maxillofac Implants. 2005;20(4):519-25.

Systematic review of implant outcomes in treated periodontitis subjects. C T Ong, S Ivanovski, I G Needleman, M Retzepi, D R Moles, M S Tonetti, J Clin Periodontol. 355Ong CT, Ivanovski S, Needleman IG, Retzepi M, Moles DR, Tonetti MS, et al. Systematic review of implant outcomes in treated periodontitis subjects. J Clin Periodontol. 2008;35(5):438-62.

1-stage versus 2-stage lateral sinus lift procedures: 1-year post-loading results of a multicentre randomised controlled trial. P Felice, R Pistilli, M Piattelli, E Soardi, C Barausse, M Esposito, Eur J Oral Implantol. 71SpringFelice P, Pistilli R, Piattelli M, Soardi E, Barausse C, Esposito M. 1-stage versus 2-stage lateral sinus lift procedures: 1-year post-loading results of a multicentre randomised controlled trial. Eur J Oral Implantol. 2014; 7(1):65-75. Spring

. N M Timmenga, G M Raghoebar, G Boering, R Van Weissenbruch, J Oral Maxillofac Surg. 55940Timmenga NM, Raghoebar GM, Boering G, van Weissenbruch R, et al. J Oral Maxillofac Surg. 1997;55(9):936-9. discussion 40

Endoscopic and ultrasonographic evaluation of the maxillary sinus after combined sinus floor augmentation and implant insertion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. J Wiltfang, S Schultze-Mosgau, H A Merten, P Kessler, A Ludwig, W Engelke, 89Wiltfang J, Schultze-Mosgau S, Merten HA, Kessler P, Ludwig A, Engelke W. Endoscopic and ultrasonographic evaluation of the maxillary sinus after combined sinus floor augmentation and implant insertion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89(3):288-91.

A clinical study of the outcomes and complications associated with maxillary sinus augmentation. A Barone, S Santini, L Sbordone, R Crespi, U Covani, Int J Oral Maxillofac Implants. 211Barone A, Santini S, Sbordone L, Crespi R, Covani U. A clinical study of the outcomes and complications associated with maxillary sinus augmentation. Int J Oral Maxillofac Implants. 2006;21(1):81-5.

Complications of intraoral donor site for bone grafting prior to implant placement. F M Silva, A L Cortez, R W Moreira, R Mazzonetto, Implant Dent. 154Silva FM, Cortez AL, Moreira RW, Mazzonetto R. Complications of intraoral donor site for bone grafting prior to implant placement. Implant Dent. 2006;15(4):420-6.

Effects of maxillary sinus floor elevation surgery on maxillary sinus physiology. N M Timmenga, G M Raghoebar, R S Liem, R Van Weissenbruch, W L Manson, A Vissink, Eur J Oral Sci. 1113Timmenga NM, Raghoebar GM, Liem RS, van Weissenbruch R, Manson WL, Vissink A. Effects of maxillary sinus floor elevation surgery on maxillary sinus physiology. Eur J Oral Sci. 2003;111(3):189-97.

Maxillary sinus membrane repair: update on technique for large and complete perforations. M A Pikos, Implant Dent. 171Pikos MA. Maxillary sinus membrane repair: update on technique for large and complete perforations. Implant Dent. 2008;17(1):24-31.

The effect of sinus membrane perforation and repair with Lambone on the outcome of maxillary sinus floor augmentation: a radiographic assessment. B Shlomi, I Horowitz, A Kahn, A Dobriyan, G Chaushu, Int J Oral Maxillofac Implants. 194Shlomi B, Horowitz I, Kahn A, Dobriyan A, Chaushu G. The effect of sinus membrane perforation and repair with Lambone on the outcome of maxillary sinus floor augmentation: a radiographic assessment. Int J Oral Maxillofac Implants. 2004;19(4):559-62.

Complication rate in 200 consecutive sinus lift procedures: guidelines for prevention and treatment. Moreno Vazquez, J C Gonzalez De Rivera, A S Gil, H S Mifsut, R S , J Oral Maxillofac Surg. 725Moreno Vazquez JC, Gonzalez de Rivera AS, Gil HS, Mifsut RS. Complication rate in 200 consecutive sinus lift procedures: guidelines for prevention and treatment. J Oral Maxillofac Surg. 2014;72(5):892-901.

Maxillary sinus floor augmentation and simultaneous implant placement using locally harvested autogenous bone chips and bone debris: a prospective clinical study. L A Johansson, S Isaksson, C Lindh, J P Becktor, L Sennerby, J Oral Maxillofac Surg. 684Johansson LA, Isaksson S, Lindh C, Becktor JP, Sennerby L. Maxillary sinus floor augmentation and simultaneous implant placement using locally harvested autogenous bone chips and bone debris: a prospective clinical study. J Oral Maxillofac Surg. 2010;68(4):837-44.

Implant surfaces and design (Working Group 4). N P Lang, S Jepsen, Clin Oral Implants Res. 204SupplLang NP, Jepsen S. Implant surfaces and design (Working Group 4). Clin Oral Implants Res. 2009;20(Suppl 4):228-31.

Effects of different implant surfaces and designs on marginal bone-level alterations: a review. I Abrahamsson, T Berglundh, Clin Oral Implants Res. 204SupplAbrahamsson I, Berglundh T. Effects of different implant surfaces and designs on marginal bone-level alterations: a review. Clin Oral Implants Res. 2009;20(Suppl 4):207-15.

Maxillary sinusfloor elevation and grafting with human demineralized freeze dried bone. J P Van Den Bergh, C M Ten Bruggenkate, G Krekeler, D B Tuinzing, Clin Oral Implants Res. 115van den Bergh JP, ten Bruggenkate CM, Krekeler G, Tuinzing DB. Maxillary sinusfloor elevation and grafting with human demineralized freeze dried bone. Clin Oral Implants Res. 2000;11(5):487-93.

Maxillary sinus elevation: the effect of macrolacerations and microlacerations of the sinus membrane as determined by endoscopy. M Aimetti, R Romagnoli, G Ricci, G Massei, Int J Periodontics Restorative Dent. 216Aimetti M, Romagnoli R, Ricci G, Massei G. Maxillary sinus elevation: the effect of macrolacerations and microlacerations of the sinus membrane as determined by endoscopy. Int J Periodontics Restorative Dent. 2001; 21(6):581-9.

Periimplant complications for posterior endosteal implants. J Esquivel-Upshaw, A Mehler, A Clark, D Neal, L Gonzaga, K Anusavice, Clin Oral Implants Res. 2612Esquivel-Upshaw J, Mehler A, Clark A, Neal D, Gonzaga L, Anusavice K. Peri- implant complications for posterior endosteal implants. Clin Oral Implants Res. 2015;26(12):1390-6.