Does physical activity modify the risk of obesity for type 2 diabetes: a review of epidemiological data

Obesity and physical inactivity are both risk factors for type 2 diabetes. Since they are strongly associated, it has been suggested that they might interact. In this study, we summarized the evidence on this interaction by conducting a systematic review. Two types of interaction have been discerned, statistical and biological interaction, which could give different results. Therefore, we calculated both types of interaction for the studies in our review. Cohort studies, published between 1999 and 2008, that investigated the effects of obesity and physical activity on the risk of type 2 diabetes were included. We calculated both biological and statistical interaction in these studies. Eight studies were included of which five were suitable to calculate interaction. All studies showed positive biological interaction, meaning that the joint effect was more than the sum of the individual effects. However, there was inconsistent statistical interaction; in some studies the joint effect was more than the product of the individual effects, in other studies it was less. The results show that obesity and physical inactivity interact on an additive scale. This means that prevention of either obesity or physical inactivity, not only reduces the risk of diabetes by taking away the independent effect of this factor, but also by preventing the cases that were caused by the interaction between both factors. Furthermore, this review clearly showed that results can differ depending on what method is used to assess interaction.     

Global Perceived Effect scales provided reliable assessments of health transition in people with musculoskeletal disorders,but ratings are strongly influenced by current status

ObjectiveThe study investigated the test–retest reliability and construct validity of the Global Perceived Effect (GPE) scale in patients with musculoskeletal disorders.Study Design and SettingData from seven clinical studies including 861 subjects were used for the analyses. Repeat measures taken at the same attendance and from attendances separated by 24 hours were compared to estimate test–retest reliability. Construct validity was evaluated by examining relationships between pre, post, and change scores in pain and disability measures with GPE measures.ResultsIntraclass correlation coefficient values of 0.90–0.99 indicate excellent reproducibility of the GPE scale. In all but one data set, change scores on pain and disability measures correlated well (r = 0.40–0.74) with GPE; however, post scores nearly always correlated even more strongly (r = 0.58–0.84), and pre scores showed much weaker association (r = 0.00–0.28). Pre scores accounted for only a small amount of additional R² when added to regression models including post score.ConclusionsTest–retest reliability of the GPE is excellent. GPE ratings are strongly influenced by current status, with the effect more obvious as transition time lengthens. This result questions whether transition ratings truly reflect change, or rather just current state. This finding also has implications for the use of GPE ratings as an external criterion of change in clinimetric studies.     

The effectiveness of ergonomic interventions on return-to-work after low back pain; a prospective two year cohort study in six countries on low back pain patients sicklisted for 3-4 months

Aims: To study occurrence and effectiveness of ergonomic interventions on return-to-work applied for workers with low back pain (LBP).

Methods: A multinational cohort of 1631 workers fully sicklisted 3–4 months due to LBP (ICD-9 codes 721, 722, 724) was recruited from sickness benefit claimants databases in Denmark, Germany, Israel, Sweden, the Netherlands, and the United States. Medical, ergonomic, and other interventions, working status, and return-to-work were measured using questionnaires and interviews at three months, one and two years after the start of sickleave. Main outcome measure was time to return-to-work. Cox's proportional hazards model was used to calculate hazard ratios regarding the time to return-to-work, adjusted for prognostic factors.

Results: Ergonomic interventions varied considerably in occurrence between the national cohorts: 23.4% (mean) of the participants reported adaptation of the workplace, ranging from 15.0% to 30.5%. Adaptation of job tasks and adaptation of working hours was applied for 44.8% (range 41.0–59.2%) and 46.0% (range 19.9–62.9%) of the participants, respectively. Adaptation of the workplace was effective on return-to-work rate with an adjusted hazard ratio (HR) of 1.47 (95% CI 1.25 to 1.72; p < 0.0001). Adaptation of job tasks and adaptation of working hours were effective on return-to-work after a period of more than 200 days of sickleave with an adjusted HR of 1.78 (95% CI 1.42 to 2.23; p < 0.0001) and 1.41 (95% CI 1.13 to 1.76; p = 0.002), respectively.

Conclusions: Results suggest that ergonomic interventions are effective on return-to-work of workers long term sicklisted due to LBP.

     

Injection drug use among street-involved youth in a Canadian setting

Background  

Street-involved youth contend with an array of health and social challenges, including elevated rates of blood-borne infections and mortality. In addition, there has been growing concern regarding high-risk drug use among street-involved youth, in particular injection drug use. We undertook this study to examine the prevalence of injection drug use and associated risks among street-involved youth in Vancouver, Canada.     

Regional pharmacokinetics of amifostine in anesthetized dogs: role of the liver, gastrointestinal tract, lungs, and kidneys.

Amifostine is a prodrug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR-1065, in normal tissues as a result of differences in membrane-bound alkaline phosphatase activity. In this study, we characterized the sites and extent of organ-specific activation by the liver, gastrointestinal tract, lungs, and kidneys after systemic administrations of amifostine. A total of 10 dogs were infused via the cephalic vein using sequential dose rates of drug at 0.125, 0.500, and 1.00 micro mol/min/kg. Infusion of each dose rate lasted 2 h, at which time steady-state plasma concentrations were obtained (i.e., portal vein, carotid artery, hepatic vein, pulmonary artery, and renal vein). The hepatic arterial, portal venous, and renal arterial blood flows, and cardiac output, were measured. The hepatic and splanchnic extraction of amifostine remained high at 90%, whereas gastrointestinal extraction decreased from 43 to 12 to 15% with increasing dose. Pulmonary extraction of amifostine was low at 7%, whereas renal extraction was intermediate at 57%. Because blood flow measurements were relatively constant during the drug infusions, clearance parameters paralleled that of organ extraction. As a result, saturability was observed in the gastrointestinal blood clearance (i.e., from 9.8 to 2.8-3.3 ml/min/kg) and total body plasma clearance of amifostine (i.e., from 52.6 to about 37.3 ml/min/kg), as the doses increased. Due to the drug's high activation in liver, these findings suggest that amifostine may offer good protection of this organ against the toxicities of chemotherapy and radiation.     

Parkinsonism in Elderly Users of Haloperidol: Associated With Dose, Plasma Concentration, and Duration of Use

ABSTRACT: Factors that influence the variation in occurrence of antipsychotic-induced parkinsonism (AIP) in the elderly have not been well elucidated. The aim of this study was to investigate the association between parkinsonism in elderly users of haloperidol and prescribed dose, plasma concentration, and duration of use of haloperidol in a cross-sectional design. This study included 150 inpatients aged 65 years and older who were treated with haloperidol. Parkinsonism assessed by the Simpson Angus Scale was present in 46% of the included patients. Prescribed haloperidol dose varied from 0.3 to 5 mg/d. Plasma concentration ranged from 0.13 to 4.11 μg/L, with one outlying measurement (21.43 μg/L). Dose is moderate but significantly associated with haloperidol plasma concentration (weighted R = 0.32; P < 0.001). Variability in the total score on the Simpson Angus Scale could not be explained by the variability in dose, concentration (respectively R = 0.003 and 0.001) nor duration of use of haloperidol. Smoking showed to be not significantly protective in the development of AIP (crude odds ratio, 0.39; 95% confidence interval, 0.15-0.997; and adjusted odds ratio, 0.44; 95% confidence interval, 0.17-1.17). In a clinical practice-setting dose, neither plasma concentration nor duration of use of haloperidol is associated with an increased occurrence of AIP. This study does not support the hypothesis of the peripheral pharmacokinetic explanation for the high prevalence of AIP and differences in AIP sensitivity in the elderly during treatment with haloperidol.     

Minimally important change determined by a visual method integrating an anchor-based and a distribution-based approach

Background: Minimally important changes (MIC) in scores help interpret results from health status instruments. Various distribution-based and anchor-based approaches have been proposed to assess MIC. Objectives: To describe and apply a visual method, called the anchor-based MIC distribution method, which integrates both approaches. Method: Using an anchor, patients are categorized as persons with an important improvement, an important deterioration, or without important change. For these three groups the distribution of the change scores on the health status instrument are depicted in a graph. We present two cut-off points for an MIC: the ROC cut-off point and the 95% limit cut-off point. Results: We illustrate our anchor-based MIC distribution method determining the MIC for the Pain Intensity Numerical Rating Scale in patients with low back pain, using two conceivable definitions of minimal important change on the anchor. The graph shows the distribution of the scores of the health status instrument for the relevant categories on the anchor, and also the consequences of choosing the ROC cut-off point or the 95% limit cut-off point. Discussion: The anchor-based MIC distribution method provides a general framework, applicable to all kind of anchors. This method forces researchers to choose and justify their choice of an appropriate anchor and to define minimal importance on that anchor. The MIC is not an invariable characteristic of a measurement instrument, but may depend, among other things, on the perspective from which minimal importance is considered and the baseline values on the measurement instrument under study. A balance needs to be struck between the practicality of a single MIC value and the validity of a range of MIC values.     

石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

石杉碱甲类似物的研究Ⅲ．N－甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲（１）是从中草药石杉属植物千层塔（ＬｙｃｏｐｏｄｉｕｍｓｅｒｒａｔｕｍＴｈｕｎｂ．）中分得的一种高效可逆的乙酰胆碱酯酶抑制剂，临床试验证实它对早老性痴呆症有显著疗效。本文报道Ｎ－甲基吡啶酮石杉碱甲类似物２和３的合成。２－甲氧基－５－甲氧羰基－１１－亚甲基－５，９－甲撑环辛－７－烯并吡啶（９）在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮１０，再用甲醇钠和碘甲烷甲基化得Ｎ－甲基吡啶酮１１，１１经碱性水解，Ｃｕｒｔｉｕｓ重排和氨基的脱保护得Ｎ－甲基吡啶酮石杉碱甲类似物２。通过类似的途径从中间体２－甲氧基－５－甲氧羰基－７－甲基－１１－酮－５，９－甲撑环辛－７－烯并吡啶（１４）合成了类似物３。类似物２和３的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。