Summary Background Metastatic DNA mismatch repair–deficient/microsatellite instability–high (dMMR/MSI-H) colorectal cancer (mCRC) has a poor prognosis following conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-infiltrating lymphocytes, and checkpoint regulators, all features that correspond with response to programmed cell death receptor-1 (PD-1) blockade in other tumour types. Thus, nivolumab, a PD-1 immune checkpoint inhibitor, was evaluated in this population. Methods In this is ongoing, multicentre, open-label, nonrandomised, phase 2 trial, adult patients (aged ≥18 years) with histologically confirmed recurrent or mCRC locally assessed as dMMR/MSI-H who had progressed on/after or been intolerant of at least one prior line of treatment, including a fluoropyrimidine and oxaliplatin or irinotecan, were enrolled. Patients were given nivolumab 3 mg/kg every 2 weeks until disease progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors v1·1. All patients who received at least one dose of study drug were included in the primary and safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02060188. Findings Among the 74 patients who were enrolled between March 12, 2014, and March 16, 2016, most (54·1%) had received ≥3 prior therapies. At a median follow-up of 12·0 months (interquartile range 8·57–18·00 months), 23 of 74 patients (31·1% [95% CI 20·8%–42·9%]) achieved an investigator-assessed objective response; 68·9% (95% CI 57·1%–79·2%) of patients had disease control for ≥12 weeks. Median duration of response was not yet reached; all responders were alive, and 8 (34·8%) had responses of ≥12 months. The most common (≥10% of patients) drug-related adverse events was fatigue (n=16 [21·6%]), diarrhoea (n=15 [20·3%]), pruritus (n=10 [13·5%]) and rash (n=8 [10·8%]). The most common grade 3 or 4 drug-related adverse events were increased lipase (n=6 [8·1%]) and amylase (n=2 [2·7%]) levels. Five patients (6·8%) discontinued treatment because of increased alanine aminotransferase, colitis, duodenal ulcer, acute kidney injury, and stomatitis (n=1 each). Twenty-three patients (31·1%) died during the study; none of these deaths was considered to be treatment related by the investigator. Interpretation Nivolumab provided durable responses and disease control, as well as long-term survival in pre-treated patients with dMMR/MSI-H mCRC, and is a new treatment option for these patients.

Less than half the persons with EM and CM were currently using preventive medication for migraine, with treatment rates being higher for CM, as expected. Those with CM tried more medications than those with EM, possibly reflecting higher levels of treatment need.

The MSQ is a reliable and valid questionnaire in the CM population that can differentiate the functional impact between CM and EM. The MSQ can assist researchers in evaluating treatment effectiveness by obtaining input directly from the patients on multidimensional aspects other than frequency of headache days.

Objective The Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) has been shown to have good psychometric performance in measuring headache impact in migraine patients, but its properties specifically in chronic migraine (CM) patients are unknown. The objective of this study was to evaluate the psychometric properties of the MSQ in a group of CM patients undergoing prophylactic treatment. Methods Measurement properties of the MSQ were examined using two international, multicenter, randomized clinical trials evaluating onabotulinumtoxinA as headache prophylaxis in CM patients (N = 1,376). Confirmatory factor analysis (CFA) was used to test the latent structure of the MSQ in CM patients. The reliability, convergent and discriminant validity, and responsiveness of the MSQ were assessed. Results CFA confirmed the currently proposed three-factor MSQ latent structure across the two studies. Good reliability was observed for all three MSQ scales, across studies and time points. MSQ scale scores strongly correlated with the scores of the Headache Impact Test-6 (HIT-6). Analysis of knowngroups validity indicated that MSQ scale scores discriminated between groups of patients differing in their 28-day headache frequency were as follows\10, 10-14, and C15 days, and the sample-derived quartiles of the total cumulative hours of headache were as follows \140, 140 to \280, 280 to \420, and C420 h (p \ 0.0001), across both studies and time points. MSQ change scores were higher in magnitude in groups experiencing greater decline in headache frequency (p \ 0.001). Conclusion The MSQ is a psychometrically valid tool that can be used to reliably measure the impact of migraine among CM patients.

Objective US general population norms for mail administration of the Medical Outcomes Study 36-Item Short Form Version 2 (SF-36v2) were established in 1998. This article reports SF-36v2 telephone-administered norms collected in 2005–2006 for adults aged 35–89 years. Study Design and Setting The SF-36v2 was administered to 3,844 adults in the National Health Measurement Study (NHMS), a random-digit dial telephone survey. Scale scores and physical and mental component summary (PCS and MCS) scores were computed. Results When compared with 1998 norms (mean = 50.00, standard deviation [SD] = 10.00), SF-36v2 scores for the 2005–2006 general population tended to be higher: physical functioning (mean = 50.68, SD = 14.48); role limitations due to physical health problems (mean = 49.47, SD = 14.71); bodily pain (mean = 50.66, SD = 16.28); general health perceptions (mean = 50.10, SD = 16.87); vitality (mean = 53.71, SD = 15.35); social functioning (mean = 51.37, SD = 13.93); role limitations due to emotional problems (mean = 51.44, SD = 13.93); mental health (mean = 54.27, SD = 13.28); PCS (mean = 49.22, SD = 15.13); MCS (mean = 53.78, SD = 13.14). PCS and MCS factor scoring coefficients were similar to those previously reported for the 1998 norms. SF-36v2 norms for telephone administration were created. Conclusion The higher scores for NHMS data are likely due to the effect of telephone administration. The 2005–2006 norms can be used as a reference to interpret scale and component summary scores for telephone-administered surveys with the SF-36v2.