Chinese Oral Cancer Patients' Pain Beliefs: An Application of Leventhal's Common-Sense Model.

BACKGROUND: Patients' pain beliefs are the main obstacle to effective pain management. Assessing and correcting negative perceptions is important for improving pain intensity and quality of life of patients with cancer pain. AIMS: To explore pain beliefs among oral cancer patients using the Common-Sense Model of Self-Regulation as a theoretical framework. The primary components of the model, cognitive representations, emotional representations, and coping responses, were examined. DESIGN: A qualitative method was used. SETTINGS: PARTICIPANTS/SUBJECTS:   METHODS: Semi-structured, qualitative, in-depth interviews were conducted with patients newly diagnosed with oral cancer in a tertiary care hospital. The interviews were analyzed using thematic analysis. RESULTS: Interviews with 15 patients revealed that the pain beliefs of patients with oral cancer included three themes: pain cognitive representations of oral cancer, pain emotional representations of oral cancer, and pain coping responses. CONCLUSIONS: Negative pain beliefs are common among oral cancer patients. This novel application of the self-regulatory model demonstrates that it can be used to capture the key pain beliefs (i.e., cognitions, emotions, and coping responses) of oral cancer patients within a single, unifying framework.

The development of a Cancer Pain Belief Modification Program for patients with oral cancer in China: a feasibility study.

BACKGROUND: Acceptance-based pain management interventions have been receiving growing attention in cancer pain care. This study aimed to develop a cancer pain management program based on belief modification to improve the cancer pain experience of Chinese oral cancer survivors and to explore the acceptability and preliminary outcomes of the Cancer Pain Belief Modification Program (CPBMP). METHODS: A mixed-methods approach was applied to develop and revise the program. The CPBMP was developed and revised using the Delphi technique, and its further improvement was explored with a one-group pre- and post-trial designed with a sample of 16 Chinese oral cancer survivors, and semi-structured interviews. Research instruments included Numeric Rating Scale (NRS), Chinese version of Illness Perception Questionnaire-Revised for Cancer Pain (IPQ-CaCP), and the University of Washington Quality of Life assessment scale (UW-QOL). Descriptive statistics, t-test, and Mann-Whitney U test were used to analyse the data. The semi-structured questions were analysed using content analysis. RESULTS: The six-module CPBMP was endorsed by most experts and patients. The expert authority coefficient value was 0.75 in the first round of the Delphi survey and 0.78 in the second round. The "pain intense", "negative pain beliefs" scores of pre- and post-testing decreased from 5.63 ± 0.48 to 0.81 ± 0.54 (t = -3.746, p < 0.001); from 140.63 ± 9.02 to 52.75 ± 7.27 (Z = 12.406, p < 0.001); and the "positive pain beliefs", "quality of life" scores increased from 55.13 ± 4.54 to 66.00 ± 4.70 (Z = -6.983, p < 0.001); from 66.97 ± 15.01 to 86.69 ± 8.42 (Z = 7.283, p < 0.001). The qualitative data also indicated that CPBMP was well acceptable. CONCLUSION: Our study showed the acceptability and preliminary outcomes of CPBMP patients. CPBMP improves the pain experience of Chinese oral cancer patients and provides a reference for cancer pain management in the future. TRIAL REGISTRATION: The feasibility study has already been registered on the Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ) in 11/09/2021. (ChiCTR2100051065).

Validation of fetal DNA fraction estimation and its application in noninvasive prenatal testing for aneuploidy detection in multiple pregnancies.

OBJECTIVE: To analyze the fetal fraction, fetal sex, and chromosomal aneuploidy in multiple pregnancies using noninvasive prenatal testing (NIPT). METHOD: A total of 362 pregnant women including 203 singleton pregnancies, 69 twins, and 90 higher-order multiple pregnancies were recruited. Fetal fractions estimated by size ratio-based and Y chromosome-based approaches in singleton pregnancies with male fetus were used as source data to establish the model. The model was then applied to multiple pregnancies for fetal fraction estimation. By comparing the fetal fractions estimated by size ratio to those estimated by Y chromosome or autosomal chromosomes, fetal sex and chromosomal aneuploidy can be analyzed. RESULTS: The size ratio-based approach has been well established in estimating fetal fractions for twin and higher-order multiple pregnancies. Fetal fraction had a positive correlation with gestational age in twin and triplet pregnancies. Fetal sex was determined with accuracies of 98.6% (95% CI, 92.19%-99.96%) in twins and 97.6% (95% CI, 91.76%-99.71%) in triplet pregnancies. Four trisomy 21, one trisomy 18, and one trisomy 13 cases were detected by NIPT. Two trisomy 21 singleton pregnancies and one trisomy 21 twin pregnancy were confirmed by karyotyping. CONCLUSION: Fetal sex and chromosomal aneuploidy in multiple pregnancies can be determined using NIPT.

A short-read multiplex sequencing method for reliable, cost-effective and high-throughput genotyping in large-scale studies.

Accurate genotyping is important for genetic testing. Sanger sequencing-based typing is the gold standard for genotyping, but it has been underused, due to its high cost and low throughput. In contrast, short-read sequencing provides inexpensive and high-throughput sequencing, holding great promise for reaching the goal of cost-effective and high-throughput genotyping. However, the short-read length and the paucity of appropriate genotyping methods, pose a major challenge. Here, we present RCHSBT-reliable, cost-effective and high-throughput sequence based typing pipeline-which takes short sequence reads as input, but uses a unique variant calling, haploid sequence assembling algorithm, can accurately genotype with greater effective length per amplicon than even Sanger sequencing reads. The RCHSBT method was tested for the human MHC loci HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1, upon 96 samples using Illumina PE 150 reads. Amplicons as long as 950 bp were readily genotyped, achieving 100% typing concordance between RCHSBT-called genotypes and genotypes previously called by Sanger sequence. Genotyping throughput was increased over 10 times, and cost was reduced over five times, for RCHSBT as compared with Sanger sequence genotyping. We thus demonstrate RCHSBT to be a genotyping method comparable to Sanger sequencing-based typing in quality, while being more cost-effective, and higher throughput.

Noninvasive prenatal testing for ß-thalassemia by targeted nanopore sequencing combined with relative haplotype dosage (RHDO): a feasibility study.

Noninvasive prenatal testing (NIPT) for single gene disorders remains challenging. One approach that allows for accurate detection of the slight increase of the maternally inherited allele is the relative haplotype dosage (RHDO) analysis, which requires the construction of parental haplotypes. Recently, the nanopore sequencing technologies have become available and may be an ideal tool for direct construction of haplotypes. Here, we explored the feasibility of combining nanopore sequencing with the RHDO analysis in NIPT of ß-thalassemia. Thirteen families at risk for ß-thalassemia were recruited. Targeted region of parental genomic DNA was amplified by long-range PCR of 10 kb and 20 kb amplicons. Parental haplotypes were constructed using nanopore sequencing and next generation sequencing data. Fetal inheritance of parental haplotypes was classified by the RHDO analysis using data from maternal plasma DNA sequencing. Haplotype phasing was achieved in 12 families using data from 10 kb library. While data from the 20 kb library gave a better performance that haplotype phasing was achieved in all 13 families. Fetal status was correctly classified in 12 out of 13 families. Thus, targeted nanopore sequencing combined with the RHDO analysis is feasible to NIPT for ß-thalassemia.

Noninvasive prenatal diagnosis of ß-thalassemia by relative haplotype dosage without analyzing proband.

BACKGROUND: ß-thalassemia is one of the most common monogenic diseases in the world. Southeast China is a highly infected area affected by four ß-thalassemia mutation types (HBB:c.-78A>G, HBB:c.52A>T, HBB:c.126_129delCTTT, and HBB:c.316-197C>T). Relative haplotype dosage (RHDO), a haplotype-based approach, has shown promise as an application for noninvasive prenatal diagnosis (NIPD); however, additional family members (such as the proband) are required for haplotype construction. The abovementioned circumstances make RHDO-based NIPD cost prohibitive; additionally, the genetic information of the proband is not always available. Thus, it is necessary to find a practical method to solve these problems. METHODS: Targeted sequencing was applied to sequence parental genomic DNA and cell-free fetal DNA (cffDNA). Parental haplotypes were constructed with the SHAPEIT software based on the 1000 Genomes Project (1000G) Phase 3 v5 Southern Han Chinese (CHS) haplotype dataset. Single-nucleotide polymorphisms (SNPs) in the target region were called and classified, and the fetal mutation inheritance status was deduced using the RHDO method. RESULTS: Construction of the parental haplotypes and detection of the inherited parental mutations were successfully achieved in five families, despite a suspected recombination event. The status of the affected fetuses is consistent with the results of traditional reverse dot blot (RDB) diagnosis. CONCLUSION: This research introduced SHAPEIT into the classical RHDO workflow and proved that it is applicable to construct parental haplotypes without information from other family members.

Effects of Maternal and Fetal Characteristics on Cell-Free Fetal DNA Fraction in Maternal Plasma.

OBJECTIVE: To study factors that influence the concentration of cell-free fetal DNA (fetal fraction) using a large clinical data set of pregnancies with male fetus. METHOD: A retrospective analysis of 23 067 pregnancies that received noninvasive prenatal testing from January 2012 to October 2013, including 22 650 normal singleton pregnancies (control group) and 417 pregnancies with aneuploidy, twin pregnancy, or various maternal conditions including preexisting hypertension, preexisting diabetes, hyperthyroidism, and carrier of the surface antigen of the hepatitis B virus (HBsAg; study group). Multiples of the median (MoM) analysis was performed in the control group to derive gestation and body mass index (BMI)-corrected fetal fraction. The effects of study group conditions on fetal fraction were examined by calculating the ratio of MoM (RMoM) values. RESULTS: Fetal fraction showed a positive correlation with gestational age (r(2) = .10, P < .001) and increased rapidly after the 21 weeks of gestation (r(2) = .26, P < .001). Negative association with maternal BMI was found with fetal fraction (r(2) = .04, P < .001). In study group, fetal fraction was higher among pregnant women with a trisomy 21 fetus (RMoM = 1.24, P < .001) and lower among trisomy 18 (RMoM = 0.84, P < .001). A 1.6-fold incensement of fetal fraction was observed in twin fetuses comparing to singleton pregnancy (RMoM = 1.62, P < .001). Women with preexisting hypertension had significantly lower fetal fraction (RMoM = 0.85, P = .02). Preexisting diabetes, hyperthyroidism, or carrier of HBsAg did not affect fetal fraction. CONCLUSION: The fetal fraction was affected by fetal aneuploidy, maternal BMI, and the number of gestation. Maternal preexisting of hypertension appeared to reduce fetal fraction.

A reliable, high-resolution and high-throughput genotyping method for HLA-DRB1.

Human leukocyte antigen (HLA) DNA typing is an essential part to identify a donor who may be a good match for the patients who need haematopoietic stem cells from bone marrow. Thus, fetching quickly high-resolution genotype is very important at present. However, current HLA DNA typing methods especially for HLA-DRB1 generally yielded ambiguous typing results because of high degree of heterozygosity on exome region and primer pairs design limitations, which generally amplified only exon2 of HLA-DRB1 and the position of its primer pairs is on exome region. To solve this problem, we developed a reliable, high-resolution and high-throughput (RHH) sequence based typing approach for HLA-DRB1 through massively parallel paired-end sequencing. Several primer pairs were designed to amplify three exon regions, which are part of exon1, the whole region of exon2 and exon3 of HLA-DRB1, to genotyping for HLA-DRB1 by synthesis. 94 samples were included to analyze and the highly successful genotyping ratio (98.94%) and no ambiguous genotyping result demonstrated the accurate performance of our method for HLA-DRB1 genotyping.