2.7 Statistical analysis
Categorical variables were described by proportions, and intergroup
differences were tested by chi-square test. Continuous variables of
normal distribution were described by means and standard deviations
(SD), and tested by one-way analysis (ANOVA) of variance. Continuous
variables of skewed distribution, including the concentrations of
arsenic in blood, urine, and hair and level of serum β-endorphin, were
described by median and interquartile range (IQR), and tested by
Kruskal-Wallis H test.
The does-response relationship between hair arsenic and NRS was
estimated by a generalized additive model with cubic spline, and
presented in figures. To
derive
parametric estimates, a multiple linear model was used for continuous
NRS score, and partial regression coefficient of hair arsenic was
reported. For dichotomous outcomes (NRS≥3 or NRS≥7), logistic models
were used, and odds ratios (ORs) with 95% confidence intervals (CIs)
were reported. Potential risk factors16 for itch were
introduced into the following models for the purpose of adjustment.
In the MR analysis, the associations of genetically predicted urinary
MMA% and DMA% with pruritus in participants of the UK Biobank was
estimated using logistic regression models, adjusting for age, sex,
race, Townsend deprivation index, smoking status and alcohol drinking.
PRSs were analyzed as either continuous or categorical (above vs. under
median) variables.
In the randomized controlled trial, an intention-to-treat (ITT) analysis
was performed to evaluate the efficacy of naloxone. The
last
observation carry-forward (LOCF) imputation method was used for
unmeasured data in drop-out participants. Mixed effect models were used
to estimate the efficacy, by constructing a model: Y =β 0+ β 1Group + β 2Time +β 3(Group×Time) + ei +υ ij, where β 2 is the
estimate for efficacy; ei andυ ij refer to the errors between individuals and
within an individual (repeated measurements), respectively.
Statistical analyses were performed in R Statistical Software 3.4.1. The
significance level for all statistical tests was 0.05.