Causal inference did not detect any effect of jump load on knee complaints in elite men's volleyball.

The aim was to determine how jump load affects knee complaints in elite men's volleyball. We collected data from four men's premier league volleyball teams through three seasons in a prospective cohort study (65 players, 102 player-seasons). Vert inertial measurement devices captured the jump load (jump frequency and jump height) from 21 088 daily player sessions, and knee complaints were reported in 3568 weekly OSTRC-O questionnaires. Mixed complementary log-log regression models described the probability of (i) experiencing symptoms if players were currently asymptomatic, (ii) worsening symptoms if players had symptoms, and (iii) recovery from knee complaints. Based on our causal assumptions, weekly jump load was modeled as the independent variable, adjusted for age (years), weight (kg), position on volleyball team, and past jump load. No certain evidence of an association was found between weekly jump load and probability of (i) knee complaints (p from 0.10 to 0.32 for three restricted cubic splines of load), (ii) worsening symptoms if the player already had symptoms (p from 0.11 to 0.97), (iii) recovery (p from 0.36 to 0.63). The probability of knee complaints was highest for above-average weekly jump load (~1.2% for an outside hitter with mean age and height) compared with low loads (~1%) and very high loads (→ ~ 0%). The association between jump load and knee complaints risk remains unclear. Small differences in risk across observed jump load levels were observed. It would likely require substantially increased sample sizes to detect this association with certainty.

A new statistical approach to training load and injury risk: separating the acute from the chronic load.

The relationship between recent (acute) training load relative to long-term (chronic) training load may be associated with sports injury risk. We explored the potential for modelling acute and chronic loads separately to address current statistical methodology limitations. We also determined whether there was any evidence of an interaction in the association between acute and chronic training loads and injury risk in football. A men's Qatar Stars League football cohort (1 465 players, 1 977 injuries), where training load was defined as the number of minutes of activity, and a Norwegian elite U-19 football cohort (81 players, 60 injuries), where training load was defined as the session rating of perceived exertion (sRPE). Mixed logistic regression was run with training load on the current day (acute load) and cumulative past training load estimated by distributed lag non-linear models (chronic load) as independent variables. Injury was the outcome. An interaction between acute and chronic training load was modelled. In both football populations, we observed that the risk of injury on the current day for different values of acute training load was highest for players with low chronic load, followed by high and then medium chronic load. The slopes varied substantially between different levels of chronic training load, indicating an interaction. Modelling acute and chronic loads separately in regression models is a suitable statistical approach for analysing the association between relative training load and injury risk in injury prevention research. Sports scientists should also consider the potential for interactions between acute and chronic load.

Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Extended Follow-Up of a 2×2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol.

BACKGROUND: Adjuvant breast cancer therapy containing anthracyclines with or without anti-human epidermal growth factor receptor-2 antibodies and radiotherapy is associated with cancer treatment-related cardiac dysfunction. In the PRADA trial (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy), concomitant treatment with the angiotensin receptor blocker candesartan attenuated the reduction in left ventricular ejection fraction (LVEF) in women receiving treatment for breast cancer, whereas the ß-blocker metoprolol attenuated the increase in cardiac troponins. This study aimed to assess the long-term effects of candesartan and metoprolol or their combination to prevent a reduction in cardiac function and myocardial injury. METHODS: In this 2×2 factorial, randomized, placebo-controlled, double-blind, single-center trial, patients with early breast cancer were assigned to concomitant treatment with candesartan cilexetil, metoprolol succinate, or matching placebos. Target doses were 32 and 100 mg, respectively. Study drugs were discontinued after adjuvant therapy. All 120 validly randomized patients were included in the intention-to-treat analysis. The primary outcome measure was change in LVEF assessed by cardiovascular magnetic resonance imaging from baseline to extended follow-up. Secondary outcome measures included changes in left ventricular volumes, echocardiographic peak global longitudinal strain, and circulating cardiac troponin concentrations. RESULTS: A small decline in LVEF but no significant between-group differences were observed from baseline to extended follow-up, at a median of 23 months (interquartile range, 21 to 28 months) after randomization (candesartan, 1.7% [95% CI, 0.5 to 2.8]; no candesartan, 1.8% [95% CI, 0.6 to 3.0]; metoprolol, 1.6% [95% CI, 0.4 to 2.7]; no metoprolol, 1.9% [95% CI, 0.7 to 3.0]). Candesartan treatment during adjuvant therapy was associated with a significant reduction in left ventricular end-diastolic volume compared with the noncandesartan group (P=0.021) and attenuated decline in global longitudinal strain (P=0.046) at 2 years. No between-group differences in change in cardiac troponin I and T concentrations were observed. CONCLUSIONS: Anthracycline-containing adjuvant therapy for early breast cancer was associated with a decline in LVEF during extended follow-up. Candesartan during adjuvant therapy did not prevent reduction in LVEF at 2 years, but was associated with modest reduction in left ventricular end-diastolic volume and preserved global longitudinal strain. These results suggest that a broadly administered cardioprotective approach may not be required in most patients with early breast cancer without preexisting cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01434134.

Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction: A Randomized, Controlled Trial.

BACKGROUND: High intake of marine n-3 polyunsaturated fatty acids (PUFA) has been associated with reduced risk of cardiovascular events; however, this has not been confirmed in patients with a recent acute myocardial infarction (AMI). Elderly patients are at particularly increased cardiovascular risk after myocardial infarction, but few trials address this group specifically. Omega-3 fatty acids hold the potential to reduce cardiovascular events with limited adverse effects in this vulnerable group. The hypothesis was that daily addition of 1.8g n-3 PUFA to standard of care secondary prophylaxis in elderly patients who have survived an AMI would reduce the risk of subsequent cardiovascular events during 2 years follow-up. METHODS: The OMEMI trial (Omega-3 Fatty acids in Elderly with Myocardial Infarction) is an investigator-initiated, multicenter, randomized clinical trial adding 1.8 g n-3 PUFA (930 mg eicosapentaenoic acid and 660 mg docosohexaenoic acid) versus placebo (corn oil) daily to standard of care in patients aged 70 to 82 years with recent (2-8 weeks) AMI. The primary endpoint was a composite of nonfatal AMI, unscheduled revascularization, stroke, all-cause death, heart failure hospitalization after 2 years. The secondary outcome was new atrial fibrillation. The safety outcome was major bleeding. Serum fatty acids were measured as biomarkers of adherence. RESULTS: In total, 1027 patients were randomized. Follow-up data were available for 1014 patients who were included in the intention-to-treat analysis. Mean±SD age was 75±3.6 years, 294 (29%) were female, and mean triglycerides were 111.4±61.9 mg/dL. The primary endpoint occurred in 108 (21.4%) patients on n-3 PUFA versus 102 (20.0%) on placebo (hazard ratio, 1.08 [95% CI, 0.82-1.41]; P=0.60). The secondary endpoint occurred in 28 (7.2%) patients on n-3 PUFA versus 15 (4.0%) on placebo (1.84 [0.98-3.45]; P=0.06). Median changes in eicosapentaenoic acid and docosahexaenoic acid were +87% and +16% for n-3 PUFA versus -13% and -8% for placebo. Major bleeding occurred in 54 (10.7%) and 56 (11.0%) in the n-3 PUFA and placebo groups, respectively (P=0.87). Similar results were found in per-protocol analysis (n=893). CONCLUSIONS: We could not detect reduction in clinical events in our elderly patients with recent AMI who were treated with 1.8 g n-3 PUFAs daily for 2 years. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01841944.

Effect of Continuous Positive Airway Pressure on Arrhythmia in Atrial Fibrillation and Sleep Apnea: A Randomized Controlled Trial.

Rationale: Sleep apnea (SA) is highly prevalent in patients with atrial fibrillation (AF), and both conditions are associated with adverse cardiovascular outcomes.Objectives: To determine the effect of continuous positive airway pressure (CPAP) on AF burden.Methods: This open-label, parallel-group, randomized controlled trial included patients with paroxysmal AF and moderate to severe SA (apnea-hypopnea index ⩾15). A computerized system randomized eligible patients (1:1) to 5 months' treatment with CPAP plus usual care (CPAP, n = 55) or usual care alone (control, n = 54). The outcome assessment was blinded. The planned primary outcome was the difference between CPAP treatment and control groups in change of AF burden (percentage of time in AF) as measured by implantable loop recorder.Measurements and Main Results: A total of 579 patients with paroxysmal AF had respiratory polygraphy, of whom 244 (42%) had moderate to severe SA. Of these, 158 (65%) participated in the CPAP run-in period, of whom 39 (25%) patients did not tolerate the treatment. A total of 108 patients were available for the primary analysis. The mean time in AF decreased from 5.6% at baseline to 4.1% during the last 3 months of CPAP intervention and from 5.0% to 4.3% in the control group. The adjusted between-group difference at follow-up was -0.63 (95% confidence interval, -2.55 to 1.30) percentage points (P = 0.52). Seven serious adverse events (13%) occurred in the CPAP group, and two (4%) occurred in the control group.Conclusions: In patients with paroxysmal AF and SA, treatment with CPAP did not result in a statistically significant reduction in the burden of AF.Clinical trial registered with www.clinicaltrials.gov (NCT02727192).

Long-Term Oncologic Outcomes After Laparoscopic Versus Open Resection for Colorectal Liver Metastases : A Randomized Trial.

BACKGROUND: Despite the recent worldwide dissemination of laparoscopic liver surgery, no high-level evidence supports the oncologic safety of this approach. OBJECTIVE: To evaluate long-term oncologic outcomes after laparoscopic versus open liver resection in patients with colorectal metastases. DESIGN: A single-center, assessor-blinded, randomized controlled trial (OSLO-COMET [Oslo Randomized Laparoscopic Versus Open Liver Resection for Colorectal Metastases Trial]). (ClinicalTrials.gov: NCT01516710). SETTING: Oslo University Hospital, the only provider of liver surgery for the 3 million inhabitants of southeastern Norway. PARTICIPANTS: Patients with resectable colorectal liver metastases were randomly assigned to have open or laparoscopic liver resection. INTERVENTION: From February 2012 to January 2016, a total of 280 patients were included in the trial (laparoscopic surgery: n = 133; open surgery: n = 147). MEASUREMENTS: The primary outcome was postoperative morbidity within 30 days. Five-year rates of overall and recurrence-free survival were predefined secondary end points. RESULTS: At a median follow-up of 70 months, rates of 5-year overall survival were 54% in the laparoscopic group and 55% in the open group (between-group difference, 0.5 percentage point [95% CI, -11.3 to 12.3 percentage points]; hazard ratio, 0.93 [CI, 0.67 to 1.30]; P = 0.67). Rates of 5-year recurrence-free survival were 30% in the laparoscopic group and 36% in the open group (between-group difference, 6.0 percentage points [CI, -6.7 to 18.7 percentage points]; hazard ratio, 1.09 [CI, 0.80 to 1.49]; P = 0.57). LIMITATION: The trial was not powered to detect differences in secondary end points and was not designed to address a noninferiority hypothesis for survival outcomes. CONCLUSION: In this randomized trial of laparoscopic and open liver surgery, no difference in survival outcomes was found between the treatment groups. However, differences in 5-year overall survival up to about 10 percentage points in either direction cannot be excluded. This trial should be followed by pragmatic multicenter trials and international registries. PRIMARY FUNDING SOURCE: The South-Eastern Norway Regional Health Authority.

Exploring cardiac effects after oxytocin 2.5 IU or carbetocin 100 µg: A randomised controlled trial in women undergoing planned caesarean delivery.

BACKGROUND: Oxytocin can stimulate release of myocardial biomarkers troponin I and T, prolong QTc and induce ST-depression. OBJECTIVE: To explore cardiac changes after either intravenous carbetocin or oxytocin. STUDY DESIGN: Exploratory phase 4 randomised controlled trial. SETTING: Obstetrics units of Oslo University Hospital, Norway between September 2015 and May 2018. PARTICIPANTS: Forty healthy, singleton pregnant women aged 18 to 50 years at gestational age at least 36 weeks with a planned caesarean delivery. INTERVENTIONS: Participants were randomised to receive either oxytocin 2.5 IU or carbetocin 100 µg immediately after delivery. MAIN OUTCOME MEASURES: The primary endpoint was the assessment of troponin I within 48 h of study drug administration. Troponin I and T, and creatine kinase myocardial band assessments were measured before spinal anaesthesia (baseline), and again at 4, 10 and 24 h after delivery. QTc, ST-depression and relative increase in heart rate were recorded from start of study drug administration to 10 min after delivery. All adverse events were monitored. RESULTS: Compared with the carbetocin group, higher troponin I levels were observed in the oxytocin group at 4 h and 10 h after delivery. For both treatment groups, an increase from baseline in troponin I and T was most pronounced at 10 h after delivery, and it had begun to decline by 24 h. QTc increased with time after administration of both study drugs, with a mean maximum increase of 10.4 ms observed at 9 min (P   <  0.001). No statistical differences were observed in QTc ( P  = 0.13) or ST-depression ( P  = 0.11) between the treatment groups. CONCLUSIONS: Oxytocin 2.5 IU and carbetocin 100 µg caused a similar increase in QTc. The trial was underpowered with regards to ST-depression and the release of myocardial biomarkers and these warrant further investigation. Data from this trial will inform a larger phase 4 trial to determine potential drug differences in troponin release. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02528136.

The longitudinal association between objectively measured physical activity and mental health among Norwegian adolescents.

BACKGROUND: Mental health among young people in many countries, including Norway, seems to be deteriorating. Physical activity (PA) has been positively associated with mental health. However, methodological issues related to study design and measurement of PA and mental health outcomes currently limits our understanding of the relationship. The purpose of the present study is to explore the prospective relationship between objectively measured PA and mental health outcomes. More specifically, volume (total PA), intensity (moderate-to-vigorous PA [MVPA]) and sedentary behaviour (SED) were explored in relation to mental health problems (MHP) and mental wellbeing (MWB). METHODS: Data from 599 adolescents (54.4% female, mean age at baseline ±SD 13.3 ± 0.3 years) were collected annually during their 3 years (T1, T2 and T3) at lower secondary school. PA was measured using accelerometry. MWB was measured using the 'Warwick-Edinburgh Mental Wellbeing Scale' and MHP by the 'Strengths and Difficulties Questionnaire'. Multiple linear regression was performed to explore relationships between changes in PA/SED (between T1-T3) and MWB/MHP (at T3). The term 'movement categories' was used to refer to components on the movement continuum and includes volume (total PA), intensity (MVPA) and SED. RESULTS: Among boys, any increase in SED was positively associated with MWB (ß = 0.05, 95% CI: 0.01 to 0.10), whereas a small positive association between an increase in total PA (volume) and MWB was found among girls (ß = 1.13, 95% CI: 0.05 to 2.21). There were no associations between changes in any movement categories [total PA (volume), MVPA, SED] and score on MHP at T3, neither for girls nor boys. CONCLUSION: This study provided no clear evidence of any association between change in volume or intensity of PA and MHP among an overall healthy adolescent study sample. There was, however, evidence of a relationship between increased SED and MWB among boys and increased volume of PA and MWB among girls. The relationship between movement categories and mental health may depend on the measurement used to assess both PA/SED and variables of mental health. Future research would be strengthened by researchers clarifying what construct of mental health is being used and measured.

Does load management using the acute:chronic workload ratio prevent health problems? A cluster randomised trial of 482 elite youth footballers of both sexes.

BACKGROUND: The acute:chronic workload ratio (ACWR) is commonly used to manage training load in sports, particularly to reduce injury risk. However, despite its extensive application as a prevention intervention, the effectiveness of load management using ACWR has never been evaluated in an experimental study. AIM: To evaluate the effectiveness of a load management intervention designed to reduce the prevalence of health problems among elite youth football players of both sexes. METHODS: We cluster-randomised 34 elite youth football teams (16 females, 18 males) to an intervention group (18 teams) and a control group (16 teams). Intervention group coaches planned all training based on published ACWR load management principles using a commercially available athlete management system for a complete 10-month season. Control group coaches continued to plan training as normal. The prevalence of health problems was measured monthly in both groups using the Oslo Sports Trauma Research Centre Questionnaire on Health Problems. RESULTS: The between-group difference in health problem prevalence (primary outcome) was 1.8%-points (-4.1 to 7.7 %-points; p=0.55) with no reduction in the likelihood of reporting a health problem in the intervention group (relative risk 1.01 (95% CI 0.91 to 1.12); p=0.84) compared with the control group. CONCLUSIONS: We observed no between-group difference, suggesting that this specific load management intervention was not successful in preventing health problems in elite youth footballers. TRIAL REGISTRATION NUMBER: ISRCTN18177140.

Accelerometer-measured physical activity and sedentary time in a cohort of US adults followed for up to 13 years: the influence of removing early follow-up on associations with mortality.

BACKGROUND: Observational studies linking physical activity with mortality are susceptible to reverse causation bias from undiagnosed and prevalent diseases. Researchers often attempt to deal with reverse causation bias by excluding deaths occurring within the first 1 or 2 years from the analysis, but it is unclear if excluding deaths within this time-frame is sufficient to remove bias. METHODS: We examined associations between total and intensity-specific physical activity and sedentary time with all-cause mortality in a prospective cohort of 3542 individuals from the 2003-2006 NHANES cycles. In order to yield measures of association hypothesized as minimally influenced by reverse causation bias the primary analysis excluded individuals with < 5 years of follow-up. Accelerometer-measured physical activity was linked with recently updated vital status from the National Death Index with a median follow-up of 10.8 years. RESULTS: Hazard ratios (95% confidence intervals) were 0.74 (0.53, 1.04), 0.52 (0.37, 0.73), and 0.61 (0.38, 1.01) for ascending quartiles of total physical activity against the least active reference. Hazard ratios for ascending moderate-to-vigorous physical activity quartiles against the reference were 0.67 (0.47, 1.96), 0.67 (0.47, 0.95), and 0.68 (0.39, 1.18). Associations for light intensity physical activity and sedentary time were smaller in magnitude and all confidence intervals included unity. Total activity and moderate-to-vigorous physical activity hazard ratios from analyses only excluding deaths within the first 2 years were inflated by 13 and 26% relative to analysis restricted to ≥5 years of follow-up. CONCLUSIONS: The pattern of associations suggested total physical activity and moderate-to-vigorous physical activity were associated with lower mortality after more than 10 years of follow-up and excluding the first 5 years of observation time to minimize the impact of reverse causation bias. Excluding deaths within the first 2 years appeared insufficient to minimize the impact of reserve causation bias.

Statement on methods in sport injury research from the 1st METHODS MATTER Meeting, Copenhagen, 2019.

High quality sports injury research can facilitate sports injury prevention and treatment. There is scope to improve how our field applies best practice methods-methods matter (greatly!). The 1st METHODS MATTER Meeting, held in January 2019 in Copenhagen, Denmark, was the forum for an international group of researchers with expertise in research methods to discuss sports injury methods. We discussed important epidemiological and statistical topics within the field of sports injury research. With this opinion document, we provide the main take-home messages that emerged from the meeting.

Statin-associated muscle symptoms in coronary patients: design of a randomized study.

Objectives. Estimate the effect of atorvastatin on muscular symptom intensity in coronary patients with subjective statin-associated muscle symptoms (SAMS) and to determine the association with blood levels of atorvastatin and its metabolites, to obtain an objective marker for true SAMS. Design. A randomized, double-blinded, cross-over study will include 80 coronary patients with subjectively reported SAMS during ongoing atorvastatin therapy or previous muscle symptoms that led to discontinuation of atorvastatin. Patients will be randomized to 7-weeks treatment with atorvastatin 40 mg/day in the first period and matched placebo in the second 7-weeks period, or placebo in the first period and atorvastatin in the second period. Each period is preceded by 1-week wash-out. A control group (n = 40) without muscle symptoms will have 7 weeks open treatment with atorvastatin 40 mg/day. Blood samples will be collected at baseline and at the end of each treatment period, and muscular symptoms will be rated by the patients weekly using a Visual Analogue Scale (VAS). The primary outcome is the difference in aggregated mean VAS scores between the last three weeks of atorvastatin treatment and of placebo treatment. The main purpose is to develop an objective marker for true SAMS, by comparing SAMS associated with blinded atorvastatin treatment with blood concentrations of atorvastatin and its metabolites. Diagnostic and discrimination performance will be determined. Conclusions. The study provides new knowledge on SAMS in coronary patients and may contribute to more personalized statin treatment and monitoring, fewer side-effects and consequently improved adherence and lipid management in future practice.

Needle tip tracking for ultrasound-guided peripheral nerve block procedures-An observer blinded, randomised, controlled, crossover study on a phantom model.

BACKGROUND: The Onvision needle tip tracking (NTT) is a new technology consisting of a needle with an ultrasound sensor close to the needle tip and a console for computerised signal processing. The aim of the study was to evaluate NTT technology during ultrasound-guided simulated peripheral nerve block procedures in a porcine phantom model. METHODS: Forty anaesthesiologists performed in-plane and out-of-plane simulated nerve blocks with and without NTT guidance. The primary outcome measure was procedure time. Secondary outcomes were hand movements and the path length travelled by the hands measured by motion analysis, precision of the needle tip related to the target structure, success rates and violations of the target structure, and the participants confidence whether their procedure would be successful or not. RESULTS: Procedure time was reduced from 66.7 (SD = 47.5) seconds to 43.8 (SD = 29.2) seconds when NTT was used for out-of-plane procedures (P = 0.002). The number of hand movements of the probe hand was 13.9 (SD = 30.2) with NTT and 22.8 (SD = 30.0) without NTT (P = 0.019). No significant differences were registered during the performance of in-plane procedures. The participants confidence in a presumed block success was increased with both in-plane procedures (8.50 (SD = 1.18) with NTT vs 7.65 (SD = 1.96), P = 0.004) and out-of-plane procedures (8.50 (SD = 1.09) vs 7.10 (SD = 1.89), P = 0.0001). CONCLUSIONS: The new NTT technology significantly reduced the procedure time and the number of hand movements for ultrasound-guided out-of-plane PNB procedures. No significant differences were found for the in-plane procedures.

The association between physical fitness level and number and severity of injury and illness in youth elite athletes.

Youth elite athletes often double their training and competition load after enrollment into specialized sport academy high school programs. The least fit athletes may be exposed to an excessive and too rapid increase in training load, with negative adaptations such as injury and illness as a consequence. In this study, our aim was to determine whether these least fit athletes were at greater risk of injury or illness during their first school year. Participants were 166 youth elite athletes (72% boys) from a variety of team, technical, and endurance sports newly enrolled into specialized sport academy high schools. The Oslo Sports Trauma Research Center Questionnaire on Health Problems was used to self-report injuries and illnesses weekly for 26 weeks. Athletes completed the Ironman Jr physical fitness test battery at baseline, evaluating endurance, strength, agility, and speed properties. We ranked the athletes based on their combined test scores and identified the least fit quartile. The main outcome was the number and severity of health problems, comparing the least fit quartile of athletes to the rest of the cohort. Overall, the least fit quartile of athletes did not report more health problems (mean 3.7, 95% CI 3.0-4.4) compared with the rest of the cohort (3.6, 3.2-3.9). In conclusion, we demonstrated no association between low physical fitness level and number and severity of injury and illness in youth elite athletes after enrollment into a specialized sport academy high school program.

Do the associations of sedentary behaviour with cardiovascular disease mortality and cancer mortality differ by physical activity level? A systematic review and harmonised meta-analysis of data from 850 060 participants.

OBJECTIVE: To examine whether the associations between sedentary behaviours (ie, daily sitting/TV-viewing time) and mortality from cardiovascular disease (CVD) and cancer differ by different levels of physical activity (PA). DESIGN: Harmonised meta-analysis of prospective cohort studies. Data on exposure variables were harmonised according to a predefined protocol and categorised into four groups for sedentary behaviours and into quartiles of PA (MET-hour/week). DATA SOURCES: PubMed, PsycINFO, Embase, Web of Science, Sport Discus and Scopus. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Individual level data on both sedentary behaviours and PA and reported effect estimates for CVD or cancer mortality. RESULTS: Nine studies (n=850 060; deaths=25 730) and eight studies (n=777 696; deaths=30 851) provided data on sitting time and CVD and cancer mortality, respectively. Five studies had data on TV-viewing time and CVD (n=458 127; deaths=13 230) and cancer (n=458 091; deaths=16 430) mortality. A dose-response association between sitting time (9%-32% higher risk; p for trend <0.001) and TV time (3%-59% higher risk; p for trend <0.001) with CVD mortality was observed in the 'inactive', lowest quartile of PA. Associations were less consistent in the second and third quartiles of PA, and there was no increased risk for CVD mortality with increasing sedentary behaviours in the most active quartile. Associations between sedentary behaviours and cancer mortality were generally weaker; 6%-21% higher risk with longer sitting time observed only in the lowest quartile of PA. CONCLUSION: PA modifies the associations between sedentary behaviours and CVD and cancer mortality. These findings emphasise the importance of higher volumes of moderate and vigorous activity to reduce, or even eliminate these risks, especially for those who sit a lot in their daily lives.

Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial.

OBJECTIVE: To perform the first randomized controlled trial to compare laparoscopic and open liver resection. SUMMARY BACKGROUND DATA: Laparoscopic liver resection is increasingly used for the surgical treatment of liver tumors. However, high-level evidence to conclude that laparoscopic liver resection is superior to open liver resection is lacking. METHODS: Explanatory, assessor-blinded, single center, randomized superiority trial recruiting patients from Oslo University Hospital, Oslo, Norway from February 2012 to January 2016. A total of 280 patients with resectable liver metastases from colorectal cancer were randomly assigned to undergo laparoscopic (n = 133) or open (n = 147) parenchyma-sparing liver resection. The primary outcome was postoperative complications within 30 days (Accordion grade 2 or higher). Secondary outcomes included cost-effectiveness, postoperative hospital stay, blood loss, operation time, and resection margins. RESULTS: The postoperative complication rate was 19% in the laparoscopic-surgery group and 31% in the open-surgery group (12 percentage points difference [95% confidence interval 1.67-21.8; P = 0.021]). The postoperative hospital stay was shorter for laparoscopic surgery (53 vs 96 hours, P < 0.001), whereas there were no differences in blood loss, operation time, and resection margins. Mortality at 90 days did not differ significantly from the laparoscopic group (0 patients) to the open group (1 patient). In a 4-month perspective, the costs were equal, whereas patients in the laparoscopic-surgery group gained 0.011 quality-adjusted life years compared to patients in the open-surgery group (P = 0.001). CONCLUSIONS: In patients undergoing parenchyma-sparing liver resection for colorectal metastases, laparoscopic surgery was associated with significantly less postoperative complications compared to open surgery. Laparoscopic resection was cost-effective compared to open resection with a 67% probability. The rate of free resection margins was the same in both groups. Our results support the continued implementation of laparoscopic liver resection.

Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women.

BACKGROUND: High amounts of sedentary behaviour have been associated with increased risks of several chronic conditions and mortality. However, it is unclear whether physical activity attenuates or even eliminates the detrimental effects of prolonged sitting. We examined the associations of sedentary behaviour and physical activity with all-cause mortality. METHODS: We did a systematic review, searching six databases (PubMed, PsycINFO, Embase, Web of Science, Sport Discus, and Scopus) from database inception until October, 2015, for prospective cohort studies that had individual level exposure and outcome data, provided data on both daily sitting or TV-viewing time and physical activity, and reported effect estimates for all-cause mortality, cardiovascular disease mortality, or breast, colon, and colorectal cancer mortality. We included data from 16 studies, of which 14 were identified through a systematic review and two were additional unpublished studies where pertinent data were available. All study data were analysed according to a harmonised protocol, which categorised reported daily sitting time and TV-viewing time into four standardised groups each, and physical activity into quartiles (in metabolic equivalent of task [MET]-hours per week). We then combined data across all studies to analyse the association of daily sitting time and physical activity with all-cause mortality, and estimated summary hazard ratios using Cox regression. We repeated these analyses using TV-viewing time instead of daily sitting time. FINDINGS: Of the 16 studies included in the meta-analysis, 13 studies provided data on sitting time and all-cause mortality. These studies included 1 005 791 individuals who were followed up for 2-18·1 years, during which 84 609 (8·4%) died. Compared with the referent group (ie, those sitting <4 h/day and in the most active quartile [>35·5 MET-h per week]), mortality rates during follow-up were 12-59% higher in the two lowest quartiles of physical activity (from HR=1·12, 95% CI 1·08-1·16, for the second lowest quartile of physical activity [<16 MET-h per week] and sitting <4 h/day; to HR=1·59, 1·52-1·66, for the lowest quartile of physical activity [<2·5 MET-h per week] and sitting >8 h/day). Daily sitting time was not associated with increased all-cause mortality in those in the most active quartile of physical activity. Compared with the referent (<4 h of sitting per day and highest quartile of physical activity [>35·5 MET-h per week]), there was no increased risk of mortality during follow-up in those who sat for more than 8 h/day but who also reported >35·5 MET-h per week of activity (HR=1·04; 95% CI 0·99-1·10). By contrast, those who sat the least (<4 h/day) and were in the lowest activity quartile (<2·5 MET-h per week) had a significantly increased risk of dying during follow-up (HR=1·27, 95% CI 1·22-1·31). Six studies had data on TV-viewing time (N=465 450; 43 740 deaths). Watching TV for 3 h or more per day was associated with increased mortality regardless of physical activity, except in the most active quartile, where mortality was significantly increased only in people who watched TV for 5 h/day or more (HR=1·16, 1·05-1·28). INTERPRETATION: High levels of moderate intensity physical activity (ie, about 60-75 min per day) seem to eliminate the increased risk of death associated with high sitting time. However, this high activity level attenuates, but does not eliminate the increased risk associated with high TV-viewing time. These results provide further evidence on the benefits of physical activity, particularly in societies where increasing numbers of people have to sit for long hours for work and may also inform future public health recommendations. FUNDING: None.

Expectations of pain and functioning in patients with musculoskeletal disorders: a cross-sectional study.

BACKGROUND: Research has suggested that patient expectations are associated with treatment outcome and evolve along with patient communication within the musculoskeletal field. However, few studies have investigated if or how physical medicine and rehabilitation (PMR) consultations affect the attending patients' expectations regarding pain and functional improvement. Hence, the aims of the present study were to compare patient expectations regarding pain and functional improvement before and after a PMR consultation and to assess patient characteristics, including diagnosis, that could perhaps predict changes in expectations. METHODS: The study design was cross-sectional. Eligible participants were first-time patients with neck/back or shoulder complaints who were referred to a PMR outpatient clinic between January and June 2013. Questionnaires (the Patient Shoulder Outcome Expectancies, or PSOE, questionnaire and a numeric rating scale, or NRS) focused on expectations regarding pain and functioning were completed immediately prior to and after a consultation with a PMR specialist. RESULTS: In total, 257 patients were included. In total, 24% of the subjects expected a more positive outcome after the PMR consultation compared with before the consultation, while 10% of the subjects exhibited a negative change in expectations. Few patient characteristics other than sick leave were associated with changes in expectations; however, patients with shoulder complaints seemed to be more optimistic than patients with neck/back complaints. CONCLUSION: Expectations can be influenced by a single specialist consultation. Among clinical prognostic factors, only sick leave influenced the change expectations. However, patients with shoulder complaints seemed to be more optimistic than patients with neck/back complaints. TRIAL REGISTRATION: The study was approved by the Data Protection Office at Oslo University Hospital, 2012/2574. ISRCTN registration: 40963362  (registered retrospectively 12.12.2016).

Pain experiences of men and women after cardiac surgery.

AIMS AND OBJECTIVES: To compare the prevalence and severity of pain in men and women during the first year following cardiac surgery and to examine the predictors of persistent postoperative pain 12 months post surgery. BACKGROUND: Persistent pain has been documented after cardiac surgery, with limited evidence for differences between men and women. DESIGN: Prospective cohort study of patients in a randomised controlled trial (N = 416, 23% women) following cardiac surgery. METHODS: Secondary data analysis of data collected prior to surgery, across postoperative days 1-4, at two weeks, and at one, three, six and 12 months post surgery. The main outcome was worst pain intensity (Brief Pain Inventory-Short Form). RESULTS: Twenty-nine percent (97/339) of patients reported persistent postoperative pain at rest at 12 months that was worse in intensity and interference for women than for men. For both sexes, a more severe co-morbidity profile, lower education and postoperative pain at rest at one month post surgery were associated with an increased probability for persistent postoperative pain at 12 months. Women with more concerns about communicating pain and a lower intake of analgesics in the hospital had an increased probability of pain at 12 months. CONCLUSION: Sex differences in pain are present up to one year following cardiac surgery. Strategies for sex-targeted pain education and management pre- and post-surgery may lead to better pain outcomes. RELEVANCE TO CLINICAL PRACTICE: These results suggest that informing patients (particularly women) about the benefits of analgesic use following cardiac surgery may result in less pain over the first year post discharge.