BackgroundOsteoarthritis of the knee is considered to be related to knee straining activities at work. The objective of this review is to assess the exposure dose-response relation between kneeling or squatting, lifting, and climbing stairs at work, and knee osteoarthritis.MethodsWe included cohort and case–control studies. For each study that reported enough data, we calculated the odds ratio (OR) per 5,000 hours of cumulative kneeling and per 100,000 kg of cumulative lifting. We pooled these incremental ORs in a random effects meta-analysis.ResultsWe included 15 studies (2 cohort and 13 case–control studies) of which nine assessed risks in more than two exposure categories. We considered all but one study at high risk of bias. The incremental OR per 5,000 hours of kneeling was 1.26 (95% confidence interval 1.17–1.35, 5 studies, moderate quality evidence) for a log-linear exposure dose-response model. For lifting, there was no exposure dose-response per 100,000 kg of lifetime lifting (OR 1.00, 95% confidence interval 1.00–1.01). For climbing, an exposure dose-response could not be calculated.ConclusionThere is moderate quality evidence that longer cumulative exposure to kneeling or squatting at work leads to a higher risk of osteoarthritis of the knee. For other exposure, there was no exposure dose-response or there were insufficient data to establish this. More reliable exposure measurements would increase the quality of the evidence.

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BackgroundMaternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions.MethodsWe analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N = 375) and self-reports (N = 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N = 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records.ResultsHigher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26–1.11, self-report: MD = 0.56 s.d.; 95% CI 0.17–0.94] and higher depressive symptoms during pregnancy (0.06 s.d. per s.d. increase; 95% CI 0.00–0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52 s.d.; 95% CI 0.12–0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p = 0.006 for interaction).ConclusionsDepression is associated with a proinflammatory state during pregnancy. These associations are mediated by early pregnancy BMI, and depressive symptoms during pregnancy aggravate the inflammation related to obesity.

PTNS is a potentially efficacious, technically simple and minimally invasive alternative treatment modality for faecal incontinence. These early results are encouraging, but we await medium- and long-term follow-up, and a larger randomised trial comparing PTNS with alternative treatments and placebo.

Rationale There has been controversy over the abuse potential of methylphenidate (MPH) in the context of treatment for attention deficit hyperactivity disorder (ADHD). Objective The objective of this study was to compare the reinforcing and subjective effects of oral MPH in adults with and without ADHD. Materials and methods Following screening, 33 adults (n= 16 with ADHD; n=17 free from psychiatric diagnoses) completed four pairs of experimental sessions, each of which included a sampling session and a self-administration session. During sampling sessions, subjects received in randomized order 0 (placebo), 20, 40, and 60 mg MPH. During self-administration sessions, subjects completed a progressive ratio (PR) task to earn portions of the dose received on the corresponding sampling session. Subjective effects were recorded throughout all sessions. The main outcome measure for the study was the number of ratios completed on the PR task. Secondary measures included peak subjective effects and area-under-the-curve values for subjective effects. Results Compared to the control group, the ADHD group completed more ratios on the PR task. Both groups showed robust effects of methylphenidate on subjective endpoints. Main effects of group were noted on subjective effects involving concentration and arousal. Conclusions Compared to placebo, MPH produced reinforcing effects only for the ADHD group and not for the control group. Increases in stimulant-related subjective effects in non-ADHD subjects were not associated with drug reinforcement.