Psychosocial factors and cancer incidence (PSY-CA): Protocol for individual participant data meta-analyses.

OBJECTIVES: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking-related, and alcohol-related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer. METHODS: The psychosocial factors and cancer incidence (PSY-CA) consortium was established involving experts in the field of (psycho-)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two-stage individual participant data (IPD) meta-analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta-analyses will be performed on the risk estimates (stage 2). CONCLUSION: PSY-CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta-analyses.

Testing Calibration of Cox Survival Models at Extremes of Event Risk.

Risk prediction models can translate genetic association findings for clinical decision-making. Most models are evaluated on their ability to discriminate, and the calibration of risk-prediction models is largely overlooked in applications. Models that demonstrate good discrimination in training datasets, if not properly calibrated to produce unbiased estimates of risk, can perform poorly in new patient populations. Poorly calibrated models arise due to missing covariates, such as genetic interactions that may be unknown or not measured. We demonstrate that models omitting interactions can lead to increased bias in predicted risk for patients at the tails of the risk distribution; i.e., those patients who are most likely to be affected by clinical decision making. We propose a new calibration test for Cox risk-prediction models that aggregates martingale residuals for subjects from extreme high and low risk groups with a test statistic maximum chosen by varying which risk groups are included in the extremes. To estimate the empirical significance of our test statistic, we simulate from a Gaussian distribution using the covariance matrix for the grouped sums of martingale residuals. Simulation shows the new test maintains control of type 1 error with improved power over a conventional goodness-of-fit test when risk prediction deviates at the tails of the risk distribution. We apply our method in the development of a prediction model for risk of cystic fibrosis-related diabetes. Our study highlights the importance of assessing calibration and discrimination in predictive modeling, and provides a complementary tool in the assessment of risk model calibration.

Validation of a novel sham cervical manipulation procedure.

BACKGROUND CONTEXT: No clinical trial of spinal manipulation for chronic neck pain (NP), for either single or multiple intervention session(s), has used an effective manual sham-manipulation control group. PURPOSE: Validate a practical sham cervical high-velocity low-amplitude spinal manipulation. STUDY DESIGN/SETTING: Randomized experimental validation study in an institutional clinical research laboratory. PATIENT SAMPLE: Eligible subjects were males and females, 18 to 60 years of age with mechanical NP (as defined by the International Association for the Study of Pain Classification) of at least 3 months' duration. Subjects with arm pain, any pathologic cause of NP, or any contraindication to spinal manipulation were excluded. OUTCOME MEASURES: The primary outcome was the patient's self-report or registration of group allocation after treatment. Secondary outcomes were numerical rating scale-101 for NP, range of motion (ROM; by goniometer), and tenderness (by pressure algometry). METHODS: Eligible subjects were randomly allocated to one of two groups: real cervical manipulation (RM) or sham cervical manipulation (SM). All subjects were given two procedures in sequence, either RM+SM or SM+SM. Immediately after the two procedures, subjects were asked to register any pain experienced during the procedures and to identify their treatment group allocation. Force-time profiles were recorded during all procedures. Secondary clinical outcome measures were obtained at baseline, 5 and 15 minutes after the intervention, including ROM, self-report of pain, and local spinous process tenderness. Data for each variable were summarized and tested for normality in distribution. Summary statistics were obtained for each variable and statistically tested. RESULTS: Sixty-seven subjects were randomized. Data from 64 subjects (32 per group) were available for analysis. There were no significant differences between the groups at baseline. One adverse event occurred in the "real" group, which was a mild posttreatment pain reaction lasting less than 24 hours. In the RM group, 50% of subjects incorrectly registered their treatment allocation; in the sham group, 53% did so. For the SM group, none of the procedures resulted in cavitation, whereas in the RM group, 87% of procedures resulted in cavitation. There were no significant changes between groups on pain, tenderness, or ROM. Force-time profiles of the RM and SM procedures demonstrated fidelity with significant differences between components as intended. CONCLUSIONS: The novel sham procedure has been shown to be effective in masking subjects to group allocation and to be clinically inert with respect to common outcomes in the immediate posttreatment stage. Further research on serial applications and for multiple operators is warranted.

A comparative analysis of sonographic interpretation of peripheral nerves in the anterior compartment of the forearm between an experienced and novice interpreter.

PURPOSE: This article describes a pilot study that compares the ability of a novice interpreter and an experienced interpreter to interpret ultrasound images of peripheral nerves in the anterior compartment of the forearm. METHODS: Twenty subjects between 18 and 50 years of age were included. A student was taken through tutorials in which she was guided through identification of the peripheral nerves of the anterior forearm. After the tutorials, the experienced interpreter traced the subjects' ulnar nerve and artery neurovascular bundle proximally in the anterior compartment of the forearm until just before it separated into the artery and nerve. Here the distance between the median and ulnar nerve was measured by the investigators. The Bland and Altman design and paired t tests were used to compare the agreement between the results of the two investigators. RESULTS: The Bland and Altman analysis reveals that the difference between two sets of measurements (experienced investigator vs. student) is calculated to be 0.08 mm ± 0.22 mm for the left arm and 0.16 mm ± 0.43 mm for the right arm. A paired t test revealed that there is no significant difference in the measurements obtained by the two investigators (left arm: p = .12; right arm: p = .10). These results suggest that the measurements of the two investigators may be interchangeable. CONCLUSIONS: This pilot study shows that after tutorials combining dissection and sonographic interpretation, the ability of a novice interpreter to identify ultrasonographic images of peripheral nerves in the anterior compartment of the forearm is comparable to that of an experienced interpreter.