Blood flow restriction augments the cross-education effect of isometric handgrip training.

INTRODUCTION: The application of blood flow restriction (BFR) to low-intensity exercise may be able to increase strength not only in the trained limb but also in the homologous untrained limb. Whether this effect is repeatable and how that change compares to that observed with higher intensity exercise is unknown. PURPOSE: Examine whether low-intensity training with BFR enhances the cross-education of strength compared to exercise without BFR and maximal efforts. METHODS: A total of 179 participants completed the 6-week study, with 135 individuals performing isometric handgrip training over 18 sessions. Participants were randomly assigned to one of four groups: 1) low-intensity (4 × 2 min of 30% MVC; LI, n = 47), 2) low-intensity with blood flow restriction (LI + 50% arterial occlusion pressure; LI-BFR, n = 41), 3) maximal effort (4 × 5 s of 100% MVC; MAX, n = 47), and 4) non-exercise control (CON, n = 44). RESULTS: LI-BFR was the only group that observed a cross-education in strength (CON: 0.64 SD 2.9 kg, LI: 0.95 SD 3.6 kg, BFR-LI: 2.7 SD 3.3 kg, MAX: 0.80 SD 3.1 kg). In the trained hand, MAX observed the greatest change in strength (4.8 SD 3.3 kg) followed by LI-BFR (2.8 SD 4.0 kg). LI was not different from CON. Muscle thickness did not change in the untrained arm, but ulna muscle thickness was increased within the trained arm of the LI-BFR group (0.06 SD 0.11 cm). CONCLUSION: Incorporating BFR into low-intensity isometric training led to a cross-education effect on strength that was greater than all other groups (including high-intensity training).

Blood flow restriction augments exercise-induced pressure pain thresholds over repetition and effort matched conditions.

We sought to determine the effects of blood flow restriction (BFR) on exercise-induced hypoalgesia, specifically using low-load (LL) resistance exercise (30% 1RM) protocols that accounted for each individual's local muscular endurance capabilities. Forty-four participants completed four conditions: (1) 70% of maximal BFR repetitions with blood flow restriction (LL+BFR exercise); (2) 70% maximal BFR repetitions without LL+BFR (LL exercise); (3) 70% maximal free flow repetitions (LL+EFFORT exercise); (4) time-matched, non-exercise control (CON). Pressure pain threshold (PPT) was measured before and after exercise. Ischaemic pain threshold and tolerance was assessed only at post. The change in upper body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.15 (0.35) kg/cm2], LL+EFFORT exercise [difference of 0.23 (0.45) kg/cm2], and the CON condition. The change in lower body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.40 (0.55) kg/cm2], LL+EFFORT exercise [difference of 0.36 (0.62) kg/cm2], and the CON condition. Ischaemic pain thresholds and tolerances did not change. Submaximal exercise with BFR resulted in systemic increases in PPT but had no influence on ischaemic pain sensitivity. This effect is likely unique to BFR as we did not see changes in the effort matched free flow condition.

Individuals Can be Taught to Sense the Degree of Vascular Occlusion: Implications for Practical Blood Flow Restriction.

ABSTRACT: Song, JS, Hammert, WB, Kataoka, R, Yamada, Y, Kang, A, and Loenneke, JP. Individuals can be taught to sense the degree of vascular occlusion: Implications for practical blood flow restriction. J Strength Cond Res 38(8): 1413-1418, 2024-It is currently unknown if individuals can be conditioned to a relative arterial occlusion pressure (AOP) and replicate that pressure at a later time point. The purpose of this study was to determine whether individuals can be taught to sense a certain relative pressure (i.e., target pressure) by comparing a conditioning method with a time-matched non-conditioning control. Fifty-eight subjects completed 2 visits in a randomized order: (a) conditioning condition and (b) time-matched control condition. The conditioning involved 11 series of inflations to 40% AOP for 12 seconds followed by cuff deflation for 22 seconds. The pressure estimations were taken at 5 and 30 minutes after each condition. Data are presented as mean differences (95% credible interval). The absolute error at 5 minutes was greater for the control compared with conditioning condition (7.1 [2.0-12.1] mm Hg). However, this difference in absolute error between conditioning and control was reduced at 30 minutes (2.9 [-1.3 to 7.1] mm Hg). The mean difference and 95% limits of agreement for the control were 8.2 (-42.4 to 58.5) mm Hg at 5 minutes and 0.02 (-43.5 to 43.5) at 30 minutes. The agreements for the conditioning were -6.2 (-32.4 to 20.0) mm Hg at 5 minutes and -11.2 (-36.6 to 14.3) mm Hg at 30 minutes. The results suggest that the individuals can be taught to sense the target pressure, but this effect only lasts a short amount of time. Future work is necessary to refine the conditioning method to extend the duration of this conditioning effect.

The Impact of Different Ischemic Preconditioning Pressures on Pain Sensitivity and Resistance Exercise Performance.

ABSTRACT: Kataoka, R, Song, JS, Yamada, Y, Hammert, WB, Seffrin, A, Spitz, RW, Wong, V, Kang, A, and Loenneke, JP. The impact of different ischemic preconditioning pressures on pain sensitivity and resistance exercise performance. J Strength Cond Res 38(5): 864-872, 2024-To determine (a) the impact of ischemic preconditioning pressures (applied as a % of arterial occlusion pressure [AOP]) on pressure pain threshold (PPT) and resistance exercise performance and (b) whether changes in performance could be explained by changes in PPT. Subjects ( n = 39) completed 4 protocols in a randomized order: (a) ischemic preconditioning (IPC) at 110% AOP (IPC 110%), (b) IPC at 150% AOP (IPC 150%), (c) IPC at 10% AOP (Sham), and (d) time-matched control (CON). Each protocol included 4 cycles of 5 minutes of occlusion followed by 5 minutes of reperfusion. Pressure pain threshold was taken before and after. Discomfort ratings were given at the end of each cycle. Every visit finished with 2 sets of 75-second maximal isokinetic unilateral elbow flexion or extension. Overall, IPC 110% and IPC 150% resulted in similar increases in PPT relative to CON [110%: difference of 0.36 (0.18, 0.54) kg·m -2 ; 150%: difference of 0.377 (0.15, 0.59) kg·m -2 ] and Sham. Both resulted in greater discomfort than Sham and CON, with IPC 150% inducing greater discomfort than IPC 110% (BF 10 : 14.74). There were no differences between the conditions for total work (BF 10 : 0.23), peak torque (BF 10 : 0.035), or average power (BF 10 : 0.159). We did not find evidence that PPT mediated performance. We did not detect changes in performance with 2 different relative pressures greater than AOP. Our mean applied pressures were lower than those used previously. There might be a minimal level of pressure (e.g., >150% of AOP) that is required to induce ergogenic effects of ischemic preconditioning.

Potential considerations with estimating blood flow restriction pressure in the lower body using a narrower cuff.

Blood flow restriction pressures are typically set as a percentage of the arterial occlusion pressure. For those who do not have the ability to measure the arterial occlusion pressure, estimation equations are available. However, notable considerations are needed when estimating pressure with a narrow cuff (5 cm) in the lower body. A previously published equation in this journal was developed but was created only using 55% of the sample because the arterial occlusion of the others could not be obtained within the manufacturer's pressure limit. The purpose of this article was twofold: (1) to investigate how previous studies have implemented the equation and (2) to highlight potential concerns of using this equation. Two databases were used to locate articles that used the equation from Loenneke et al. (2015). We found that this equation had been cited 10 times to estimate arterial occlusion pressure with some notable concerns. Some did not use a 5 cm wide cuff, while others used it for participants who had arterial occlusion pressures exceeding 300 mmHg. To highlight the latter, we also applied the Loenneke et al. (2015) lower body equation to participants with arterial occlusion pressures known to exceed 300 mmHg to demonstrate potential concerns. This retrospective analysis found that 52% of the sample with known pressures over 300 mmHg (40 out of 77) would be estimated below 300 mmHg. This paper highlighted important considerations for those trying to estimate arterial occlusion pressure in the lower body with a narrow cuff (5 cm).

Clinical Evaluation of Portable Wound Volumetric Measurement Devices.

OBJECTIVE: Wound dimensional assessments are important in determining the progress of a wound and the effect of interventions on wound healing. The FastSCAN (FS; Polhemus Inc, Colchester, Vermont) and Silhouette Mobile (SM; ARANZ Medical, Christchurch, New Zealand) are portable devices that quantify surface area, depth, and volume of wounds. This study evaluated their reliability in producing accurate wound measurements. DESIGN AND SETTING: This study was conducted at the Waikato Hospital, Hamilton, New Zealand. PATIENTS AND INTERVENTION: Eleven vascular patients with a combined total of 16 wounds underwent simultaneous wound measurements using three-dimensional computed tomography (CT) reconstruction, FS, and SM. MAIN OUTCOME MEASURE: The validity of FS and SM was tested against CT. Additionally, the interoperator reliability and intraoperator reliability of FS and SM were determined. MAIN RESULTS: The intraoperator reliability and interoperator reliability for volume recordings of the SM were 0.97 and 0.97, respectively, and for the FS were 0.96 and 0.97, respectively. The FS and SM measurements were not significantly different from CT. The SM consistently produced smaller wound volume and depth measurements compared with CT. In contrast, overestimation was observed for FS when compared with CT. However, the volume measurements in one wound were anomalous, being 10 times larger than CT measurements. Excluding this wound, there were strong correlations in wound volumes for SM and CT (r = 0.81; P ≤ .0001), for FS and CT (r = 0.99; P ≤ .001), and for SM and FS (r = 0.99; P ≤ .0001). CONCLUSIONS: Measurements from FS and SM were comparable to CT. Therefore, SM and FS devices both offer the benefit of being noncontact portable devices that produce reproducible and reliable readings.

The current state of phage therapy in livestock and companion animals.

In a global context, bacterial diseases caused by pathogenic bacteria have inflicted sustained damage on both humans and animals. Although antibiotics initially appeared to offer an easy treatment for most bacterial infections, the recent rise of multidrug-resistant bacteria, stemming from antibiotic misuse, has prompted regulatory measures to control antibiotic usage. Consequently, various alternatives to antibiotics are being explored, with a particular focus on bacteriophage (phage) therapy for treating bacterial diseases in animals. Animals are broadly categorized into livestock, closely associated with human dietary habits, and companion animals, which have attracted increasing attention. This study highlights phage therapy cases targeting prominent bacterial strains in various animals. In recent years, research on bacteriophages has gained considerable attention, suggesting a promising avenue for developing alternative substances to antibiotics, particularly crucial for addressing challenging bacterial diseases in the future.

Cross-Education of Muscular Endurance: A Scoping Review.

BACKGROUND: It is well established that performing unilateral resistance training can increase muscle strength not only in the trained limb but also in the contralateral untrained limb, which is widely known as the cross-education of strength. However, less attention has been paid to the question of whether performing unilateral resistance training can induce cross-education of muscular endurance, despite its significant role in both athletic performance and activities of daily living. OBJECTIVES: The objectives of this scoping review were to provide an overview of the existing literature on cross-education of muscular endurance, as well as discuss its potential underlying mechanisms and offer considerations for future research. METHODS: A scoping review was conducted on the effects of unilateral resistance training on changes in muscular endurance in the contralateral untrained limb. This scoping review was conducted in PubMed, SPORTDiscus, and Scopus. RESULTS: A total of 2000 articles were screened and 21 articles met the inclusion criteria. Among the 21 included studies, eight studies examined the cross-education of endurance via absolute (n = 6) or relative (n = 2) muscular endurance test, while five studies did not clearly indicate whether they examined absolute or relative muscular endurance. The remaining eight studies examined different types of muscular endurance measurements (e.g., time to task failure, total work, and fatigue index). CONCLUSION: The current body of the literature does not provide sufficient evidence to draw clear conclusions on whether the cross-education of muscular endurance is present. The cross-education of muscular endurance (if it exists) may be potentially driven by neural adaptations (via bilateral access and/or cross-activation models that lead to cross-education of strength) and increased tolerance to exercise-induced discomfort. However, the limited number of available randomized controlled trials and the lack of understanding of underlying mechanisms provide a rationale for future research.

The Plateau in Muscle Growth with Resistance Training: An Exploration of Possible Mechanisms.

It is hypothesized that there is likely a finite ability for muscular adaptation. While it is difficult to distinguish between a true plateau following a long-term training period and short-term stalling in muscle growth, a plateau in muscle growth has been attributed to reaching a genetic potential, with limited discussion on what might physiologically contribute to this muscle growth plateau. The present paper explores potential physiological factors that may drive the decline in muscle growth after prolonged resistance training. Overall, with chronic training, the anabolic signaling pathways may become more refractory to loading. While measures of anabolic markers may have some predictive capabilities regarding muscle growth adaptation, they do not always demonstrate a clear connection. Catabolic processes may also constrain the ability to achieve further muscle growth, which is influenced by energy balance. Although speculative, muscle cells may also possess cell scaling mechanisms that sense and regulate their own size, along with molecular brakes that hinder growth rate over time. When considering muscle growth over the lifespan, there comes a point when the anabolic response is attenuated by aging, regardless of whether or not individuals approach their muscle growth potential. Our goal is that the current review opens avenues for future experimental studies to further elucidate potential mechanisms to explain why muscle growth may plateau.

Dietary L-Methionine modulates the gut microbiota and improves the expression of tight junctions in an in vitro model of the chicken gastrointestinal tract.

BACKGROUND: The poultry industry encounters a number of factors that affect growth performance and productivity; nutrition is essential for sustaining physiological status and protecting against stressors such as heat, density, and disease. The addition of vitamins, minerals, and amino acids to the diet can help restore productivity and support the body's defense mechanisms against stress. Methionine (Met) is indispensable for poultry's energy metabolism, physiology, performance, and feed utilization capacity. Through this study, we aimed to examine the physiological effects of methionine supplementation on poultry as well as alterations of intestinal microbiome. METHODS: We utilized the DL- and L- form of methionine on Caenorhabditis elegans and the FIMM (Fermentor for intestine microbiota model) in-vitro digesting system. A genomic-analysis of the transcriptome confirmed that methionine supplementation can modulate growth-related physiological metabolic pathways and immune responses in the host poultry. The C. elegans model was used to assess the general health benefits of a methionine supplement for the host. RESULTS: Regardless of the type or concentration of methionine, supplementation with methionine significantly increased the lifespan of C. elegans. Feed grade L-Methionine 95%, exhibited the highest lifespan performance in C. elegans. Methionine supplementation increased the expression of tight junction genes in the primary intestinal cells of both broiler and laying hens, which is directly related to immunity. Feed grade L-Methionine 95% performed similarly or even better than DL-Methionine or L-Methionine treatments with upper doses in terms of enhancing intestinal integrity. In vitro microbial cultures of healthy broilers and laying hens fed methionine revealed changes in intestinal microflora, including increased Clostridium, Bacteroides, and Oscillospira compositions. When laying hens were given feed grade L-Methionine 95% and 100%, pathogenic Campylobacter at the genus level was decreased, while commensal bacteria were increased. CONCLUSIONS: Supplementation of feed grade L-Methionine, particularly L-Methionine 95%, was more beneficial to the host poultry than supplementing other source of methionine for maintaining intestinal integrity and healthy microbiome.

Dietary supplementation with probiotics promotes weight loss by reshaping the gut microbiome and energy metabolism in obese dogs.

Obesity and overweight among companion animals are significant concerns, paralleling the issues observed in human populations. Recent research has highlighted the potential benefits of various probiotics in addressing weight-related changes, obesity, and associated pathologies. In this study, we delved into the beneficial probiotic mechanisms in high-fat-induced obese canines, revealing that Enterococcus faecium IDCC 2102 (IDCC 2102) and Bifidobacterium lactis IDCC 4301 (IDCC 4301) have the capacity to mitigate the increase in body weight and lipid accumulation in obese canines subjected to a high-fat diet and hyperlipidemic Caenorhabditis elegans (C. elegans) strain VS29. Both IDCC 2102 and IDCC 4301 demonstrated the ability to reduce systemic inflammation and hormonal disruptions induced by obesity. Notably, these probiotics induced modifications in the microbiota by promoting lactic acid bacteria, including Lactobacillaceae, Ruminococcaceae, and S24-7, with concomitant activation of pyruvate metabolism. IDCC 4301, through the generation of bacterial short-chain fatty acids and carboxylic acids, facilitated glycolysis and contributed to ATP synthesis. Meanwhile, IDCC 2102 produced bacterial metabolites such as acetic acid and butyric acid, exhibiting a particular ability to stimulate dopamine synthesis in a canine model. This stimulation led to the restoration of eating behavior and improvements in glucose and insulin tolerance. In summary, we propose novel probiotics for the treatment of obese animals based on the modifications induced by IDCC 2102 and IDCC 4301. These probiotics enhanced systemic energy utilization in response to high caloric intake, thereby preventing lipid accumulation and restoring stability to the fecal microbiota. Consequently, this intervention resulted in a reduction in systemic inflammation caused by the high-fat diet.IMPORTANCEProbiotic supplementation affected commensal bacterial proliferation, and administering probiotics increased glycolysis and activated pyruvate metabolism in the body, which is related to propanate metabolism as a result of pyruvate metabolism activation boosting bacterial fatty acid production via dopamine and carboxylic acid specialized pathways, hence contributing to increased ATP synthesis and energy metabolism activity.

Blood flow restriction pressure for narrow cuffs (5 cm) cannot be estimated with precision.

Blood flow restriction pressures are set relative to the lowest pressure needed to occlude blood flow with that specific cuff. Due to pressure limitations of some devices, it is often not possible to occlude blood flow in all subjects and apply a known relative pressure in the lower body with a 5 cm wide cuff.Objective. To use a device capable of generating high pressures (up to 907 mmHg) to create and validate an estimation equation for the 5 cm cuff in the lower body using a 12 cm cuff.Approach. 170 participants had their arterial occlusion pressure (AOP) with a 5 cm and 12 cm cuff and their thigh circumference measured in their right leg. The sample was randomly allocated to a prediction group (66%) and validation group (33%). Thigh circumference and 12 cm AOP were used as predictors. A Bland-Altman plot was constructed to assess agreement between measured and predicted values.Main results. The mean difference (95% confidence interval) between the observed (336.8 mmHg) and the predicted (343.9 mmHg) 5 cm AOP was 7.1 (-11.9, 26.1) mmHg. The 95% limits of agreement were -133.6 to 147.8 mmHg. There was a negative relationship between the difference and the average of predicted and measured 5 cm AOP (B= -0.317,p= 0.000043).Significance. Although this was the first study to quantify AOP over 600 mmHg with a 5 cm cuff, our equation is not valid across all levels of pressure. If possible, larger cuff widths should be employed in the lower body.

Can we improve exercise-induced hypoalgesia with exercise training? An overview and suggestions for future studies.

Exercise-induced hypoalgesia refers to a reduction in pain sensitivity following a single bout of exercise, which has been shown to be diminished or impaired with aging and chronic pain. Exercise training (repeated bouts of exercise over time) is often recommended as a non-pharmacological treatment for chronic pain and age-related functional declines. However, whether exercise training can augment the exercise-induced hypoalgesia has not been well studied. The purpose of this paper is to 1) provide an overview of the existing literature investigating the effect of exercise training on the magnitude of exercise-induced hypoalgesia, and 2) discuss potential underlying mechanisms as well as considerations for future research. Given the paucity of randomized controlled trials in this area, the effects of exercise training on exercise-induced hypoalgesia are still unclear. Several potential mechanisms have been proposed to explain the impaired exercise-induced hypoalgesia in chronic pain and older individuals (e.g., endogenous opioid, cardiovascular, and immune system). Exercise training appears to induce physiological changes in those systems, however, further investigations are necessary to test whether this will lead to improved exercise-induced hypoalgesia. Future research should consider including a time- and age-matched non-training group and utilizing the same exercise protocol for testing exercise-induced hypoalgesia across intervention groups.

Combination Treatment of Arazyme and Soy Leaf Extract Attenuates Hyperglycemia and Hepatic Steatosis in High-Fat Diet-Fed C57BL/6J Mice.

Arazyme and extracts of soy leaves (ESLs) are used as ingredients for functional foods; however, their combined administration has not been studied. This study assessed the combined effect of Arazyme and ESLs in high-fat-diet (HFD)-induced obese C57BL/6J mice fed 2 mg/kg Arazyme, 50 mg/kg ESLs, or a combination of 2 mg/kg Arazyme and 50 mg/kg ESLs by oral gavage for 13 weeks. Individually, Arazyme and ESLs had no effect on the HFD-induced phenotypes. The combination of Arazyme and ESLs significantly suppressed body weight gain, improved glucose and insulin tolerance, and suppressed hepatic steatosis by reducing lipid synthesis and enhancing lipid utilization gene expression. Furthermore, the combination significantly reduced HFD-induced plasma bile acid reabsorption by suppressing bile acid transporter expression, including the ATP biding cassette subfamily B member 11 (Abcb11), solute carrier family 10 member 1 (Slc10a1), Slc10a2, Slc51a, and Slc51b in the liver and gut. Moreover, the combination of Arazyme and ESLs significantly prevented HFD-induced islet compensation in the pancreas. These results suggest that the incorporation of Arazyme combined with ESLs reduces HFD-induced body weight, hyperglycemia, and hepatic steatosis by regulating liver-gut bile acid circulation in HFD-fed mice. This combination can markedly reduce treatment doses and enhance their therapeutic effects, thereby reducing therapeutic healthcare costs.

Systematic review identified suboptimal reporting and use of race/ethnicity in general medical journals.

OBJECTIVE: Methods of reporting of race/ethnicity in biomedical journals are largely unknown. We aimed to systematically examine the reporting practice of race/ethnicity and socioeconomic status (SES) information in biomedical journals. STUDY DESIGN AND SETTING: All primary research articles that reported more than one racial/ethnic group, published between 1999 and 2003 in Annals of Internal Medicine, JAMA, The Lancet, and The New England Journal of Medicine (n=1,152) were reviewed for their use of race/ethnicity and SES variables. Interobserver reliability was assessed by independent abstraction of 10% of study sample. RESULTS: There were a total of 116 different terms used to describe various racial/ethnic groups. Assignment of race/ethnicity by self-report was stated in only 13% of papers; 52% of papers identifying race/ethnicity of study participants did not report any SES information. Overall, 16% of articles explicitly stated reasons for collecting information on race/ethnicity. CONCLUSION: Our results suggest that race/ethnicity information was suboptimally reported in general medical journals. Terminology used was highly variable. Method of establishing racial/ethnic categories, rationale for collecting race/ethnicity data, and SES information were underreported.

Cinnamomum cassia Prevents High-Fat Diet-Induced Obesity in Mice through the Increase of Muscle Energy.

The cortex of Cinnamomum cassia Presl (Cinnamomi Cortex: CC) has commonly been used for weight control in traditional medicines, but without a scientific basis. Therefore, this study was undertaken to investigate the anti-obesity effect of CC extract in a high-fat diet (HFD)-induced obese mouse model and in C2C12 mouse skeletal muscle cells. Male C57BL/6 mice were fed a normal diet or a HFD for 16 consecutive weeks, and orally administered CC extract (100 or 300[Formula: see text]mg/kg) or metformin (250[Formula: see text]mg/kg; positive control) daily for 16 weeks. CC extract administration significantly decreased body weights, food intakes, and serum levels of glucose, insulin, total cholesterol and ALT levels, prevented oral glucose tolerance and insulin resistance, inhibited the protein expressions of MyHC and PGC1[Formula: see text] and the phosphorylation of AMPK, suppressed lipid accumulation in liver, decreased adipocyte size and increased muscle mass in obese mice. For this in vitro study, C2C12 myoblasts were differentiated into the myotubes for five days, and then treated with CC extract (0.1 or 0.2[Formula: see text]mg/ml) for 24[Formula: see text]h. CC extract significantly increased ATP levels by increasing the mRNA expressions of mitochondrial biogenesis-related factors, such as, PGC1[Formula: see text], NRF-1, and Tfam, and the phosphorylations of AMPK and ACC. Our results suggest CC extract controls weight gain in obese mice by inhibiting lipid accumulation and increasing energy expenditure, and that its action mechanism involves the up-regulation of mitochondrial biogenesis in skeletal muscle cells.

The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer.

BACKGROUND: Over the past decade, a number of new therapeutic agents have become available in the treatment of metastatic breast cancer (MBC). This study characterized the use and assessed the impact on survival of population-based access to new agents for the treatment of MBC. METHODS: The dates of release in British Columbia of 7 new systemic agents for MBC during the 1990s were used to construct 4 time cohorts. All patients with a first diagnosis of distant metastases in each of the time cohorts were identified and characterized, and their survival was compared. Cox proportional regression modeling was used to assess for predictors of survival. RESULTS: In total, 2150 patients with a first distant metastases diagnosed during 1 of the 4 cohort intervals were identified. Baseline characteristics between cohorts were similar, except a greater proportion of the later cohorts received adjuvant chemotherapy (P < .001), had positive estrogen receptor status (P = .01), and had a longer median time from initial diagnosis to MBC (P < .001). Survival in Cohort 1 (1991-1992) and Cohort 2 (1994-1995; median, 438 days and 450 days, respectively) was similar. Survival was longer in Cohort 3 (1997-1998; median, 564 days; P = .002) and improved further in Cohort 4 (1999-2001; median, 667 days; P = .05). In multivariate analysis, the later cohorts were associated independently with improved survival (P = .01 and P < .001, respectively). CONCLUSIONS: Population-based access to new therapeutic agents for MBC appeared to be associated with improved survival. To the authors' knowledge, this is the first study to date that demonstrates, from a population-based perspective, improving survival over the past decade for women with MBC.