Decompression with or without Fusion in Degenerative Lumbar Spondylolisthesis.

BACKGROUND: In patients with lumbar spinal stenosis and degenerative spondylolisthesis, it is uncertain whether decompression surgery alone is noninferior to decompression with instrumented fusion. METHODS: We conducted an open-label, multicenter, noninferiority trial involving patients with symptomatic lumbar stenosis that had not responded to conservative management and who had single-level spondylolisthesis of 3 mm or more. Patients were randomly assigned in a 1:1 ratio to undergo decompression surgery (decompression-alone group) or decompression surgery with instrumented fusion (fusion group). The primary outcome was a reduction of at least 30% in the score on the Oswestry Disability Index (ODI; range, 0 to 100, with higher scores indicating more impairment) during the 2 years after surgery, with a noninferiority margin of -15 percentage points. Secondary outcomes included the mean change in the ODI score as well as scores on the Zurich Claudication Questionnaire, leg and back pain, the duration of surgery and length of hospital stay, and reoperation within 2 years. RESULTS: The mean age of patients was approximately 66 years. Approximately 75% of the patients had leg pain for more than a year, and more than 80% had back pain for more than a year. The mean change from baseline to 2 years in the ODI score was -20.6 in the decompression-alone group and -21.3 in the fusion group (mean difference, 0.7; 95% confidence interval [CI], -2.8 to 4.3). In the modified intention-to-treat analysis, 95 of 133 patients (71.4%) in the decompression-alone group and 94 of 129 patients (72.9%) in the fusion group had a reduction of at least 30% in the ODI score (difference, -1.4 percentage points; 95% CI, -12.2 to 9.4), showing the noninferiority of decompression alone. In the per-protocol analysis, 80 of 106 patients (75.5%) and 83 of 110 patients (75.5%), respectively, had a reduction of at least 30% in the ODI score (difference, 0.0 percentage points; 95% CI, -11.4 to 11.4), showing noninferiority. The results for the secondary outcomes were generally in the same direction as those for the primary outcome. Successful fusion was achieved with certainty in 86 of 100 patients (86.0%) who had imaging available at 2 years. Reoperation was performed in 15 of 120 patients (12.5%) in the decompression-alone group and in 11 of 121 patients (9.1%) in the fusion group. CONCLUSIONS: In this trial involving patients who underwent surgery for degenerative lumbar spondylolisthesis, most of whom had symptoms for more than a year, decompression alone was noninferior to decompression with instrumented fusion over a period of 2 years. Reoperation occurred somewhat more often in the decompression-alone group than in the fusion group. (NORDSTEN-DS ClinicalTrials.gov number, NCT02051374.).

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.

Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. OBJECTIVE: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). DESIGN: Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028). SETTING: Eight Scandinavian referral centers. PATIENTS: From 1998 to 2005, 191 patients with mild PHPT were included. INTERVENTION: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). MEASUREMENTS: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. RESULTS: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). LIMITATION: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. CONCLUSION: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. PRIMARY FUNDING SOURCE: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.

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.

Monitoring Simvastatin Adherence in Patients With Coronary Heart Disease: A Proof-of-Concept Study Based on Pharmacokinetic Measurements in Blood Plasma.

BACKGROUND: Poor statin adherence remains a public health concern associated with adverse outcomes. We evaluated the use of pharmacokinetic measurements to monitor adherence to simvastatin in patients with coronary heart disease (CHD). METHODS: Eighteen patients with CHD taking an evening dose of simvastatin 20 mg (n = 7), 40 mg (n = 5), or 80 mg (n = 6) were examined at steady-state pharmacokinetics. Ten patients were instructed to interrupt simvastatin dosing and return for blood sampling for the subsequent 3 days. Dose-normalized plasma concentrations of simvastatin lactone and simvastatin acid and the sum of the 2 were evaluated to discriminate between adherent dosing and dose omission. Bioanalytical quantification was performed using liquid chromatography-tandem mass spectrometry. RESULTS: A simvastatin acid cutoff of 1.0 × 10 -2 nmol -1 ·L -1 ·mg -1 identified 100% of those omitting 2 doses and 60% of those omitting a single dose. Simvastatin acid showed superior ability to discriminate dose omission, as well as the best agreement between samples handled at ambient and cool temperatures (median deviation 3.5%; interquartile range -2.5% to 13%). The cutoff for a morning dose schedule, with a similar ability to discriminate, was estimated at 2.0 × 10 -3 nmol -1 ·L -1 ·mg -1 . CONCLUSIONS: The present method discriminated between adherence and reduced adherence to simvastatin therapy in patients with CHD. Sample handling is feasible for routine practice, and the assessment of adherence can be performed by direct measurement of simvastatin acid in a blood sample, according to defined cutoff values. Further studies validating the cutoff value and utility for clinical application are encouraged.

Exercise-induced change in circulating NT-proBNP could not distinguish between patients with and without coronary artery disease: the CADENCE study.

Objective. In patients with chest pain, exercise stress test has a moderate accuracy for coronary artery disease (CAD). Adding a reliable cardiac biomarker to the exercise test could potentially improve the precision of the test. We investigated circulating NT-proBNP levels before and during exercise stress test in patients with and without angiographically verified CAD. We hypothesized that NT-proBNP would give an additive diagnostic value to the exercise stress test. Methods. In patients presenting with symptoms of stable CAD, venous blood samples were taken at rest and within 5 min of termination of a maximal stress test on a bicycle ergometer. All study participants underwent coronary angiography. Significant CAD was defined as ≥75% stenosis in one or more segments of the coronary arteries. Results. Of the 297 participants, significant CAD was found in 111 (37%) patients. Resting levels of NT-proBNP were significantly higher in patients with CAD compared with patients without CAD (74.18 vs. 56.03 ng/L), p = .005. During exercise, NT-proBNP levels increased in the total population (p < .001). The rise was, however, not significantly different between the two groups (8.24 vs. 8.51 ng/L), p = .700. Combining resting NT-proBNP with positive exercise stress test was superior to exercise test alone in predicting CAD, AUC = 0.68 vs. 0.64. Conclusion. Exercise-induced change in circulating NT-proBNP could not distinguish between patients with or without CAD. However, resting levels of NT-proBNP were significantly higher in patients with CAD than those without CAD.

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.

Device-measured physical activity, adiposity and mortality: a harmonised meta-analysis of eight prospective cohort studies.

BACKGROUND: The joint associations of total and intensity-specific physical activity with obesity in relation to all-cause mortality risk are unclear. METHODS: We included 34 492 adults (72% women, median age 62.1 years, 2034 deaths during follow-up) in a harmonised meta-analysis of eight population-based prospective cohort studies with mean follow-up ranging from 6.0 to 14.5 years. Standard body mass index categories were cross-classified with sample tertiles of device-measured total, light-to-vigorous and moderate-to-vigorous physical activity and sedentary time. In five cohorts with waist circumference available, high and low waist circumference was combined with tertiles of moderate-to-vigorous physical activity. RESULTS: There was an inverse dose-response relationship between higher levels of total and intensity-specific physical activity and mortality risk in those who were normal weight and overweight. In individuals with obesity, the inverse dose-response relationship was only observed for total physical activity. Similarly, lower levels of sedentary time were associated with lower mortality risk in normal weight and overweight individuals but there was no association between sedentary time and risk of mortality in those who were obese. Compared with the obese-low total physical activity reference, the HRs were 0.59 (95% CI 0.44 to 0.79) for normal weight-high total activity and 0.67 (95% CI 0.48 to 0.94) for obese-high total activity. In contrast, normal weight-low total physical activity was associated with a higher risk of mortality compared with the obese-low total physical activity reference (1.28; 95% CI 0.99 to 1.67). CONCLUSIONS: Higher levels of physical activity were associated with lower risk of mortality irrespective of weight status. Compared with obesity-low physical activity, there was no survival benefit of being normal weight if physical activity levels were low.

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.

Dietary changes in early-stage breast cancer patients from pre-surgery and over the 12 months post-surgery.

The time after a breast cancer diagnosis is a potential period for making positive dietary changes, but previous results are conflicting. The main aim of the present study was to study breast cancer patients' dietary changes during the 12 months post-surgery and from 12 months pre-surgery to 12 months post-surgery with repeated administration of a 7-d pre-coded food diary and an FFQ, respectively. Women (n 506), mean age 55·3 years diagnosed with invasive breast cancer (stages I and II), were included. The dietary intake was quite stable over time, but the intake was lower for energy (0·3 and 0·4 MJ/d), alcohol (1·9 and 1·5 g/d) and vegetables (17 and 22 g/d) at 6 months than 3 weeks post-surgery (food diary) and at 12 months post-surgery than pre-surgery (FFQ), respectively. Furthermore, energy percentage (E%) from carbohydrates increased between 0·8 and 1·2 E% and E% from fat decreased between 0·6 and 0·8 E% over time, measured by both dietary assessment methods. We observed a higher intake of dairy products (11 g/d) at 6 months post-surgery (food diary), and a lower intake of dairy products (34 g/d) and red and processed meat (7·2 g/d) at 12 months post-surgery (FFQ). Moreover, 24 % of the patients claimed they made dietary changes, but mostly they did not change their diet differently compared with those patients who claimed no changes. In conclusion, breast cancer patients reported only minor dietary changes from 12 months pre-surgery and during the 12 months post-surgery.

Clinical and psychological factors in coronary heart disease patients with statin associated muscle side-effects.

BACKGROUND: To compare clinical and psychological factors among patients with self-perceived statin-associated muscle symptoms (SAMS), confirmed SAMS, and refuted SAMS in coronary heart disease patients (CHD). METHODS: Data were obtained from a cross-sectional study of 1100 CHD outpatients and a study of 71 CHD outpatients attending a randomized, double-blinded, placebo-controlled, crossover study to test effects of atorvastatin 40 mg/day on muscle symptom intensity. Clinical and psychosocial factors were compared between patients with and without SAMS in the cross-sectional study, and between patients with confirmed SAMS and refuted SAMS in the randomized study. RESULTS: Bilateral, symmetric muscle symptoms in the lower extremities during statin treatment were more prevalent in patients with confirmed SAMS compared to patients with refuted SAMS (75% vs. 41%, p = 0.01) in the randomized study. No significant differences in psychological factors (anxiety, depression, worry, insomnia, type D personality characteristics) were detected between patients with and without self-perceived SAMS in the cross-sectional study, or between patients with confirmed SAMS and refuted SAMS, in the randomized study. CONCLUSIONS: Patients with confirmed SAMS more often present with bilateral lower muscle symptoms compared to those with refuted SAMS. Psychological factors were not associated with self-perceived SAMS or confirmed SAMS. A careful pain history and a search for alternative causes of muscle symptoms are likely to promote communication in patients with SAMS, and may reduce the risk for statin discontinuation.

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.

Step by step: Association of device-measured daily steps with all-cause mortality-A prospective cohort Study.

INTRODUCTION: Walking is free, does not require special training, and can be done almost everywhere. Therefore, walking is a feasible behavior on which to tailor public health messages. This study assesses the prospective association and dose-response relationship between daily steps and all-cause mortality. MATERIALS AND METHODS: Daily steps were measured by waist-mounted accelerometers in 2183 individuals (53% women) for seven consecutive days at baseline (2008-09). Participants were followed for a median period of 9.1 years and associations between steps and all-cause mortality determined by registry linkage were assessed using Cox proportional hazard regression with adjustment for relevant covariates. RESULTS: Mean age was 57.0 (SD 10.9) years at baseline. Median (IQR) daily steps across ascending quartiles were 4651 (3495-5325), 6862 (6388-7350), 8670 (8215-9186), and 11 467 (10 556-13 110), respectively. During follow-up, 119 individuals died (68% men). Higher number of daily steps was associated with a lower risk of all-cause mortality with hazard ratios of 1.00 (referent), 0.52 (0.29-0.93), 0.50 (0.27-0.94), and 0.43 (0.21-0.88) across ascending quartiles of daily steps in the multivariable-adjusted model with follow-up commencing 2 years after baseline. Risk differences per 1000 individuals for ascending quartiles were 6.8 (2.9-9.3), 7.1 (0.8-11.1), and 8.0 (1.7-12.1), respectively. CONCLUSIONS: Daily steps were associated with lower mortality risk in a non-linear dose-response pattern. The risk is almost halved when comparing the least active referent against the second quartile equivalent to a difference of about 2200 daily steps. Encouraging those least active to increase their daily steps may have substantial public health implications.

Joint associations of accelero-meter measured physical activity and sedentary time with all-cause mortality: a harmonised meta-analysis in more than 44 000 middle-aged and older individuals.

OBJECTIVES: To examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality. METHODS: We conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.0 to 14.5 years during which 3451 participants died (7.8% mortality rate). Associations between different combinations of moderate-to-vigorous intensity physical activity (MVPA) and sedentary time were analysed at study level using Cox proportional hazards regression analysis and summarised using random effects meta-analysis. RESULTS: Across cohorts, the average time spent sedentary ranged from 8.5 hours/day to 10.5 hours/day and 8 min/day to 35 min/day for MVPA. Compared with the referent group (highest physical activity/lowest sedentary time), the risk of death increased with lower levels of MVPA and greater amounts of sedentary time. Among those in the highest third of MVPA, the risk of death was not statistically different from the referent for those in the middle (16%; 95% CI 0.87% to 1.54%) and highest (40%; 95% CI 0.87% to 2.26%) thirds of sedentary time. Those in the lowest third of MVPA had a greater risk of death in all combinations with sedentary time; 65% (95% CI 1.25% to 2.19%), 65% (95% CI 1.24% to 2.21%) and 263% (95% CI 1.93% to 3.57%), respectively. CONCLUSION: Higher sedentary time is associated with higher mortality in less active individuals when measured by accelerometry. About 30-40 min of MVPA per day attenuate the association between sedentary time and risk of death, which is lower than previous estimates from self-reported data.

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.