A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Metabolic Factors Limiting Performance in Marathon Runners

Each year in the past three decades has seen hundreds of thousands of runners register to run a major marathon. Of those who attempt to race over the marathon distance of 26 miles and 385 yards (42.195 kilometers), more than two-fifths experience severe and performance-limiting depletion of physiologic carbohydrate reserves (a phenomenon known as ‘hitting the wall’), and thousands drop out before reaching the finish lines (approximately 1–2% of those who start). Analyses of endurance physiology have often either used coarse approximations to suggest that human glycogen reserves are insufficient to fuel a marathon (making ‘hitting the wall’ seem inevitable), or implied that maximal glycogen loading is required in order to complete a marathon without ‘hitting the wall.’ The present computational study demonstrates that the energetic constraints on endurance runners are more subtle, and depend on several physiologic variables including the muscle mass distribution, liver and muscle glycogen densities, and running speed (exercise intensity as a fraction of aerobic capacity) of individual runners, in personalized but nevertheless quantifiable and predictable ways. The analytic approach presented here is used to estimate the distance at which runners will exhaust their glycogen stores as a function of running intensity. In so doing it also provides a basis for guidelines ensuring the safety and optimizing the performance of endurance runners, both by setting personally appropriate paces and by prescribing midrace fueling requirements for avoiding ‘the wall.’ The present analysis also sheds physiologically principled light on important standards in marathon running that until now have remained empirically defined: The qualifying times for the Boston Marathon

Increasing Dietary Fat Elicits Similar Changes in Fat Oxidation and Markers of Muscle Oxidative Capacity in Lean and Obese Humans

In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m2, age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m2, 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity

It’s Better with Salt: Aqueous Ring-Opening Metathesis Polymerization at Neutral pH

Aqueous ring-opening metathesis polymerization (ROMP) is a powerful tool for polymer synthesis under environmentally-friendly conditions, functionalization of biomacromolecules, and preparation of polymeric nanoparticles via ROMP-induced self-assembly (ROMPISA). Whilst new water-soluble Ru-based metathesis catalysts have been developed and evaluated for their efficiency in mediating cross metathesis (CM) and ring-closing metathesis (RCM) reactions, less is known with regards to their catalytic activity and stability during aqueous ROMP. Here, we investigate the influence of solution pH, the presence of salt additives, and catalyst loading on key parameters typically utilized to assess polymerizations such as monomer conversion, molecular weight, and molecular weight distribution. We find that ROMP in aqueous media is particularly sensitive to chloride ion concentration, and propose that this sensitivity originates from chloride ligand displacement by hydroxide or H_{2}O at the Ru center which reversibly generates an unstable and metathesis inactive complex. The formation of this Ru-(OH)n complex not only reduces monomer conversion and polymerization control but also influences polymer microstructure. However, we find that addition of chloride salts dramatically improves ROMP conversion and control. By carrying out aqueous ROMP in the presence of various chloride sources such as NaCl, KCl, or tetrabutylammonium chloride, we show that di- and triblock polymers can be readily synthesized in solutions with high concentrations of neutral H_{2}O (i.e., 90 v/v%) and relatively low concentrations of catalyst (i.e., 1 mol%). The capability to conduct well-controlled aqueous ROMP at neutral pH is anticipated to enable new research avenues, particularly for applications in biological media, where the unique characteristics of ROMP provide distinct advantages over other polymerization strategies

Metformina interage com o treinamento físico diminuindo a glicemia e aumentando o armazenamento de glicogênio em ratos diabéticos Metformin interacts with physical training decreasing glycemia and increasing glycogen supply in diabetic rats

INTRODUÇÃO: Assim como em humanos, ratos diabéticos apresentam baixas quantidades de glicogênio. Entretanto, treinamento ou medicamentos podem causar diminuição da glicemia e melhorar o controle metabólico. Metformina aumenta o glicogênio enquanto diminui a glicemia em ratos normais estressados por exercício. OBJETIVO: Investigar se exercício regular e metformina melhoram o metabolismo de ratos diabéticos. MÉTODOS: Ratos Wistar diabéticos por aloxana tratados com metformina (DTM) ou não (DT) foram treinados. O treinamento consistiu de 20 sessões de 30 min de duração, cinco dias por semana. Ratos diabéticos sedentários foram usados como controle (SD e SDM). Metformina (5,6µg/ml) foi dada na água de beber. Após 48h de repouso, a glicose (mg/dl) e a insulina (ng/mL) foram medidas no plasma e o glicogênio (mg/100mg de tecido molhado) no fígado, sóleo e gastrocnêmio. RESULTADOS: A glicemia diminuiu de 435 ± 15 para 230 ± 20 no grupo DSM, para 143 ± 8,1 no grupo DT e para 138 ± 19mg/dl no grupo DTM. O grupo DSM teve proporcional aumento de glicogênio hepático de 1,69 ± 0.22 para 3,53 ± 0.24 e o treinamento aumentou para 3,36 ± 0,16mg/100mg. A metformina induziu aumento proporcional nos músculos sóleo de 0,21 ± 0,008 para 0,42 ± 0,03 e no gastrocnêmio, de 0,33 ± 0,02 para 0,46 ± 0,03, enquanto que o treinamento aumentou apenas no gastrocnêmio para 0,53 ± 0,03. Uma grande interação foi observada no fígado (o glicogênio aumentou para 6,48 ± 0,34). CONCLUSÃO: Pequenas doses orais de metformina e/ou treinamento restituíram parcialmente a glicemia e promoveram aumento de glicogênio em tecidos de ratos diabéticos. A associação com o programa de exercício foi benéfica, ajudando a diminuir a glicemia e a aumentar o armazenamento de glicogênio no fígado de ratos diabéticos.<br>INTRODUCTION: Like in humans, lower amounts of glycogen are present in tissues of diabetic rats. However, training or drugs that lower glycemia can improve the metabolic control. Metformin increased glycogen while decreased glycemia in normal rats stressed by exercise. OBJECTIVE: In this work we investigated if regular exercise and metformin effects improve the metabolism of diabetic rats. METHODS: Alloxan diabetic Wistar rats treated with metformin (DTM) or not (DT) were trained. Training consisted of 20 sessions of 30 min, 5 days a week. Sedentary diabetic rats served as control (SD and SDM). Metformin (5.6 µg/g) was given in the drinking water. After 48 h resting, glucose (mg/dl) and insulin (ng/mL) was measured in plasma and glycogen (mg/100 mg of wet tissue) in liver, soleus and gastrocnemius. RESULTS: Glycemia decreased in DM group from 435±15 to 230±20, in DT group to 143±8.1 and in DTM group to 138±19 mg/dl. DM group had proportional increase in the hepatic glycogen from 1.69±0.22 to 3.53±0.24, and the training increased to 3.36 ± 0.16 mg/100 mg. Metformin induced the same proportional increase in the muscles (soleus from 0.21±0.008 to 0.42±0.03 and gastrocnemius from 0.33±0.02 to 0.46±0.03), while the training promoted increase on gastrocnemius to 0,53 ± 0,03, only. A high interaction was observed in liver (glycogen increased to 6.48±0.34). CONCLUSION: Very small oral doses of metformin and/or, partially restored glycemia in diabetic rats and decreased glycogen in tissues. Its association with an exercise program was beneficial, helping lower glycemia further and increase glycogen stores on liver of diabetic rats