A model‐based procedure for assessing the extent to which missing data can be ignored and handling non‐ignorable missing data is presented. The procedure is based on item response theory modelling. As an example, the approach is worked out in detail in conjunction with item response data modelled using the partial credit and generalized partial credit models. Simulation studies are carried out to assess the extent to which the bias caused by ignoring the missing‐data mechanism can be reduced. Finally, the feasibility of the procedure is demonstrated using data from a study to calibrate a medical disability scale.

Stress plays an important role in the development of visceral hypersensitivity, a key mechanism underlying the pathophysiology of the irritable bowel syndrome. Visceral sensitivity in rats is generally assessed under restrain conditions. To avoid this potential stress factor, we developed a model using implanted radio telemetry for remote measurement of the visceromotor response (VMR) to colorectal distention (CRD). Ten days after implantation of a radio telemetry transmitter and EMG electrodes, visceral sensitivity was evaluated by applying a standardized distension protocol (1, 1.5 and 2 mL) on three different days. In a second series, visceral sensitivity was assessed in maternally separated rats before, directly after and at 6 and 24 h after water avoidance (WA) stress. CRD resulted in a reproducible VMR response on the three different study days. In separated but not in non-handled rats, WA significantly increased visceral sensitivity at 6 h (P=0.006) and 24 h (P=0.004) after WA. Our results show that radio telemetry is a reliable and well tolerated new tool for evaluating visceral sensitivity in rats. These data further confirm that maternal separation is a good model for evaluating the mechanisms underlying visceral hypersensitivity.

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To investigate the natural history and prognostic factors in patients with nonhereditary, adultonset progressive muscular atrophy. Design: Inception cohort conducted for 18 months. Settings: Three university hospitals in the Netherlands (referral centers for neuromuscular diseases). Patients: Thirty-seven consecutive patients newly diagnosed (onset of weakness Ͻ4 years) with progressive muscular atrophy enrolled between 1998 and 2001. Main Outcome Measures: Disease progression was measured at 0, 3, 6, 9, 12, 15, and 18 months by the Medical Research Council sum score, number of affected limb regions, and the Amyotrophic Lateral Sclerosis Functional Rating Scale score. Multivariate linear regression analysis was used to identify predictors of poor outcome. Clinical features and classification of phenotype during follow-up were evaluated. Survival analysis was planned after data collection, performed 5 years after the end of the study. Results: Significant decline of muscle strength (mean, 6.01 Medical Research Council sum score points [95% confidence interval [CI], 3.84-8.18]; P value Ͻ.001) and significant increase in the number of affected regions (mean, 0.53 affected region [95% CI, 0.42-0.65]; P value Ͻ.001) and functional impairment (mean, 1.85 Amyotrophic Lateral Sclerosis Functional Rating Scale score points [95% CI, 1.38-2.33]; P value Ͻ.001) were found. Vital capacity (VC) at baseline and decrease of VC during the first 6 months were significantly associated with outcome. Median survival duration after initial weakness was 56 months. Conclusions: This study shows that patients with progressive muscular atrophy have a relentlessly progressive disease course. Patients with a low VC at baseline and a sharp decline of VC during the first 6 months have an especially poor prognosis.

Short-term fructose consumption, in isocaloric exchange or in hypercaloric supplementation, promotes the development of hepatic insulin resistance in nondiabetic adults without affecting peripheral or muscle insulin sensitivity. Larger and longer-term studies are needed to assess whether real-world fructose consumption has adverse effects on insulin sensitivity and long-term outcomes.