Prevalence of repeat faecal immunochemical testing in symptomatic patients attending primary care.

AIM: The faecal immunochemical test (FIT) for faecal haemoglobin (f-Hb) helps determine the risk of colorectal cancer (CRC) and has been integrated into symptomatic referral pathways. 'Safety netting' advice includes considering referral for persistent symptoms, but no published data exists on repeated FITs. We aimed to examine the prevalence of serial FITs in primary care and CRC risk in these patients. METHOD: A multicentre, retrospective, observational study was conducted of patients with two or more consecutive f-Hb results within a year from three Scottish Health Boards which utilize FIT in primary care. Cancer registry data ensured identification of CRC cases. RESULTS: Overall, 135 396 FIT results were reviewed, of which 12 359 were serial results reported within 12 months (9.1%), derived from 5761 patients. Of these, 42 (0.7%) were diagnosed with CRC. A total of 3487 (60.5%) patients had two f-Hb < 10 µg/g, 944 (16.4%) had f-Hb ≥ 10 µg/g followed by <10 µg/g, 704 (12.2%) f-Hb < 10 µg/g followed by ≥10 µg/g and 626 (10.9%) had two f-Hb ≥ 10 µg/g. The CRC rate in each group was 0.1%, 0.4%, 1.4% and 4.0%, respectively. Seven hundred and thirty four patients submitted more than two FITs within a year. The likelihood of one or more f-Hb ≥ 10 µg/g rose from 40.4% with two samples to 100% with six, while the CRC rate fell from 0.8% to 0%. CONCLUSION: Serial FITs within a year account for 9.1% of all results in our Boards. CRC prevalence amongst symptomatic patients with serial FIT is lower than in single-FIT cohorts. Performing two FITs within a year for patients with persistent symptoms effectively acts as a safety net, while performing more than two within this timeframe is unlikely to be beneficial.

Supporting the patients with advanced cancer and their family caregivers: what are their palliative care needs?

BACKGROUND: The impact and consequences of cancer on the patients and their family caregivers (FCs) are closely intertwined. Caregivers' burdens can be increased due to the patients' unmet needs and unresolved problems. Additionally, the caregivers' unmet needs may adversely affect their own well-being and the patients' health outcomes. This study aims to determine the palliative care needs and the factors associated with these needs in patients with advanced solid cancer and their FCs. METHODS: In a cross-sectional survey, 599 patients with advanced solid tumours and 599 FCs were recruited from the largest ambulatory cancer centre and the inpatient ward of the largest hospital in Singapore. Determinants of patients' and FCs' needs were assessed by the Comprehensive Needs Assessment Tool (CNAT) and CNAT-C respectively. Clinical characteristics of patients were obtained from medical records. RESULTS: The FCs (median age 51 years) were younger than the patients (median age 62 years), and were mostly female (62.6%) whereas the gender distribution of patients was quite balanced (49.2% male and 50.8% female). Both patients and FCs had "information" and "practical support" in their top three domains of palliative care needs. The second highest domain of needs was "psychological problems" (16.4 ± 21.5) in patients and "health-care staff" (23.4 ± 26.5) in FCs. The item that had the highest need score in "information" domain for both patients and FCs was "financial support for patients, either from government and/ or private organizations". Under clinical setting, the inpatients (19.2 ± 16.4) and their FCs (26.0 ± 19.0) tend to have higher needs than the outpatients (10.5 ± 12.1) and their FCs (14.7 ± 14.3). In terms of palliative care, higher total CNAT score was observed in both patients (16.6 ± 12.9 versus 13.3 ± 15.2) and their FCs (25.1 ± 18.6 versus 17.7 ± 16.7) who received palliative care. In terms of patients' KPS scores, patients with lower KPS scores tend to have higher needs. CONCLUSION: Overall, the findings confirm that patients with advanced cancer and their FCs have many palliative care needs irrespective of their clinical settings. Initiatives and interventions for the development of a comprehensive support system for both patients with advanced cancer and their FCs are warranted and can be derived from these findings.

Validation of the Comprehensive Needs Assessment Tool in Patients with Advanced Cancer.

AIMS: The 59-item Comprehensive Needs Assessment Tool (CNAT) for cancer patients is an English language survey developed in South Korea. The objective of this study was to validate the English version of CNAT in advanced cancer patients in Singapore. METHODS: This was a cross-sectional survey where advanced cancer patients completed the CNAT in English. Confirmatory factor analysis was used to assess construct validity. For known groups validity, independent samples t-test was used to compare CNAT scores based on the Karnofsky performance status and outpatient versus inpatient setting. Cronbach's alpha was used to measure internal consistency. RESULTS: A total of 328 advanced cancer patients were recruited. The mean age was 59.6 years and 49.1% were male. Majority (68.0%) were Chinese, 20.4% were Malay, 7.9% were Indian, and 3.7% were of other ethnicities. The 7-factor model previously established in Korea showed sufficient construct validity with root mean square error of approximation 0.037 and comparative fit index 0.944. All 59 items had a factor loading ≥0.5. Group invariance test showed no difference in the pattern of factor loadings between ethnic Chinese and other ethnic groups (P = 0.155). For known groups validity, there were significant differences in CNAT scores by performance status and outpatient versus inpatient setting. The CNAT total and factor scores showed good internal consistency with Cronbach's alpha of between 0.80 and 0.937. CONCLUSIONS: The CNAT showed construct and known-group validity and internal consistency in this study sample and can be used to assess the unmet needs of advanced cancer patients in the Singapore context.

Facilitating terminal discharge: fulfilling the hospitalised patient's wish for home death in the final hours.

BACKGROUND: Terminal discharge (TD) is the rapid discharge of a hospitalised patient when death is imminent. Its time-limited nature makes it challenging, particularly for ward nurses. AIM: To report the development of a structured TD framework, and determine if the framework can expedite TD processes and improve nurses' experience in conducting TDs. METHODS: A 3-phase audit was carried out in a Singapore hospital. The baseline and post intervention audits evaluated the time taken for TD, incidence of prescription errors, continuity of care, and timeliness of equipment arrangement. Nurse satisfaction was assessed through a written survey. Interventions encompassed the implementation of workflow changes and a TD guide. RESULTS: The mean time taken to complete TDs was shorter in the post-compared to pre-intervention phase (2.9±1.4 vs. 4.6±2.3 hours respectively, p<0.01). Approximately 89% of nurses who used the TD guide were satisfied that it made TDs easier. CONCLUSION: A structured TD framework is effective in expediting TDs and improving nurse satisfaction.

Quality of life domains important and relevant to family caregivers of advanced cancer patients in an Asian population: a qualitative study.

PURPOSE: This study aims to identify domains of quality of life (QoL) that are culturally relevant to Chinese caregivers of advanced cancer patients in Singapore and to evaluate content adequacy of currently available instruments for use in the target population. METHODS: English- and Chinese-speaking caregivers of advanced cancer patients receiving care under a tertiary cancer center and/or a community hospice home care/day care provider were recruited for in-depth interviews. The interviews were analyzed using thematic analysis. The identified domains, themes and sub-themes were compared to concepts addressed by items from five existing cancer-specific caregiver QoL instruments. RESULTS: Eighteen female and eight male caregivers aged 28-74 years participated in the study. Twenty-nine QoL themes and 59 sub-themes were identified in six domains, namely physical health, mental health, social health, spiritual health, financial health and daily life. Collectively, but not individually, the content of the five existing instruments adequately cover the physical health domain, social health domain and some themes on mental health domain for the study population. Content gaps were identified in the domains of mental health, spiritual health, daily life and financial health. CONCLUSIONS: The present study found culturally and contextually specific themes and sub-themes about positive emotional health, spiritual health and financial health.

Alternative diagnoses and demographics associated with a raised quantitative faecal immunochemical test in symptomatic patients.

BACKGROUND: The faecal immunochemical test (FIT) has proven utility for colorectal cancer detection in symptomatic patients. However, most patients with a raised faecal haemoglobin (f-Hb) do not have colorectal cancer. We investigated alternative diagnoses and demographics associated with a raised f-Hb in symptomatic patients. METHODS: A retrospective, observational study was performed of patients with FIT submitted between August 2018 to January 2019 in NHS Greater Glasgow and Clyde followed by colonoscopy. Colonoscopy/pathology reports were searched for alternative diagnoses. Covariables were compared using the χ2 test. Multivariate binary logistic regression identified independent predictors of a raised f-Hb. RESULTS: 1272 patients were included. In addition to colorectal cancer (odds ratio (OR), 9.27 (95% confidence interval (CI): 3.61-23.83; p < 0.001)), older age (OR, 1.52 (95% CI: 1.00-2.32; p = 0.05)), deprivation (OR, 1.54 (95% CI: 1.21-1.94; p < 0.001)), oral anticoagulants (OR, 1.78 (95% CI: 1.01-3.15; p = 0.046)), rectal bleeding (OR, 1.47 (95% CI: 1.15-1.88; p = 0.002)), advanced adenoma (OR, 7.52 (95% CI: 3.90-14.49; p < 0.001)), non-advanced polyps (OR, 1.78 (95% CI: 1.33-2.38; p < 0.001)) and inflammatory bowel disease (IBD) (OR, 4.19 (95% CI: 2.17-8.07; p < 0.001)) independently predicted raised f-Hb. Deprivation (Scottish Index of Multiple Deprivation (SIMD) 1-2: OR, 2.13 (95% CI: 1.38-3.29; p = 0.001)) independently predicted a raised f-Hb in patients with no pathology found at colonoscopy. CONCLUSIONS: An elevated f-Hb is independently associated with older age, deprivation, anticoagulants, rectal bleeding, advanced adenoma, non-advanced polyps and IBD in symptomatic patients. Deprivation is associated with a raised f-Hb in the absence of pathology. This must be considered when utilising FIT in symptomatic patients.

Mapping the English and Chinese versions of the Functional Assessment of Cancer Therapy-General to the EQ-5D utility index.

OBJECTIVE: This study aims to develop a function for mapping the English and Chinese versions of the Functional Assessment of Cancer Therapy-General (FACT-G) scores to the EuroQoL Group's EQ-5D utility index and to test whether a single function is sufficient for the two language versions. METHODS: A baseline survey of 558 cancer patients in Singapore using the FACT-G and EQ-5D was conducted (308 English and 250 Chinese questionnaires). Regression models were used to predict the EQ-5D utility index values based on the FACT-G scores and thus derive a mapping equation. Data from a follow-up survey of the patients were used to validate the results. RESULTS: The FACT-G Social/Family scale was not associated with the EQ-5D utility index (P = 0.701). There was no interaction between language version and the predictors (each P > 0.1). An equation that maps the FACT-G Physical, Emotional, and Functional well-being scales to the EQ-5D utility index was derived. In the validation sample, the mean observed utility values was larger than the mapped by only 0.005 (95% confidence interval [CI]-0.006 to 0.016), but the mean absolute difference was 0.083 (95% CI 0.076 to 0.090). CONCLUSIONS: At the group level, but not individual level, the equation developed can accurately map the English and Chinese versions of the FACT-G scores to the EQ-5D utility index.

An 11-Year Study of Home Hospice Service Trends in Singapore from 2000 to 2010.

BACKGROUND: Hospice care is most appropriate when a patient no longer benefits from curative treatment and has limited life expectancy. These patients may suffer from any type of life-limiting illness, including end-stage cancer, end-stage heart disease, end-stage renal failure, AIDS, and Alzheimer's disease, among other illnesses. Patients are managed on their pain and symptoms and home hospice care manages these patients in the comfort of their own home, enabling patients to spend their last days with dignity and have a good quality of life. OBJECTIVE: To describe the home hospice patients at HCA Hospice Care (HHC) Singapore from 2000 to 2010. Description of home care patients in terms of their sociodemographic profile and diagnosis at admission. We reviewed the Electronic Medical Records of patients admitted into HHC from 2000 to 2010. RESULTS: Patients had multiple admissions into HHC home hospice as identified in the Electronic Medical Records (EMR) between January 1, 2000, and December 31, 2010, but we only selected patient's first admission into HHC home hospice for this analysis. Of the 25,065 patients in the entire samples, 47.3% were males, 65.2% were married, and 84.3% were Chinese. 50.9% of the patients died at home, 75.5% were referred from public hospitals, 53.9% of primary caregivers were children, and the mean age of the patients was 68.0 years. Among all cancer patients admitted into HHC home hospice, lung cancer (23.6%) was the most common principal diagnosis for admission, followed by colorectal (10.5%) and liver cancers (7.7%). Among noncancer patients, renal failure (7.0%) was the most common diagnosis. Among male patients admitted into HHC home hospice, lung cancer (29.6%) was the most common diagnosis, followed by liver cancer (10.8%), colorectal cancer (10.0%), and end-stage renal failure (5.5%). For female patients, lung cancer (16.9%) was the most common diagnosis, followed by breast cancer (15.9%), colorectal cancer (11.0%), and end-stage renal failure (8.7%). Ten-year trends of the sociodemographic profile and diagnosis at admission were further analyzed to determine home hospice services utilization and the needs of the home care patients. CONCLUSION: With an increasing emphasis to encourage aging and dying in the community and more attention given to building up the home hospice industry's capacity and capability, it is important to understand the profile of the patients who have been utilizing home hospice services. This also helps to plan and develop similar services in other parts of the world.

Caregiving and Its Resulting Effects-The Care Study to Evaluate the Effects of Caregiving on Caregivers of Patients with Advanced Cancer in Singapore.

Informal caregivers (IC) are key to enabling home deaths, where preferred, at the end-of-life. Significant morbidity from advanced cancer can make caregiving burdensome. However, knowledge about the nature of the caregiving burden for caregivers in Singapore is limited. Hence, the key objective in this study was to examine the impact of the caregiving burden on quality of life (QOL), mental health and work capacity among local ICs. Eligible English-speaking ICs of hospitalized advanced cancer patients were recruited through non-random sampling. The Zarit Burden Interview (ZBI), Caregiver Quality of Life Index-Cancer (CQOLC), Center for Epidemiologic Studies Depression Scale-Revised (CESD-R), and Work Productivity and Activity Impairment Questionnaire (WPAI) were interviewer-administered to eligible ICs. Altogether, 16 ICs were surveyed. The mean age of ICs was 43.8 years. Most were children of patients (43.8%), and eight ICs had high burden (ZBI > 17). Those with ZBI > 17 had lower QOL, higher depression scores as well as greater work and activity impairment. In conclusion, high caregiver burden has adverse effects on QOL, mental health and work productivity. Non-physical elements of caregiving (particularly financial and decision-making) and increased number of care roles undertaken by a single IC contribute to high burden. Future interventions for caregiving burden in Singapore should also address the financial and decision-making aspects of caregiving. Outsourcing selected aspects of the caregiving role to community services may reduce the number of caregiving aspects undertaken by a single IC and caregiver burden.

A Quantitative Framework Classifying the Palliative Care Workforce into Specialist and Generalist Components.

BACKGROUND: Early referral to palliative care (PC) services has been shown to improve quality of life in advanced cancer. However, limitations in trained PC workforce raise issues with the sustainability of delivering PC with early PC referral. Classifying PC into generalist and specialist components could be one approach to sustainable PC delivery models but a quantitative guide for this classification is presently lacking in the literature. OBJECTIVE: To undertake a retrospective examination of clinical data obtained from a PC benchmarking project to develop a quantitative framework guiding classification of PC services into specialist and generalist components. DESIGN: A descriptive retrospective study of data from 2726 hospitalized inpatients under the care of a tertiary consultative PC service over a 2-year period was conducted. Daily categorical symptom, overall psychological and social distress scores at the start and end of 3392 palliative care episodes as well as the number of visits made by the PC team to patients were extracted for analysis. RESULTS: More than 50% of patients had symptom, overall psychological or social distress scores of nil or mild severity at episode start and end. Approximately 20% of all 2726 patients accounted for approximately half of all visits made by the team regardless of the reasons for review. This patient percentage minority had more PC episodes starting with moderate or severe pain. These findings suggest a Pareto-like distribution in the occurrence of moderate/severe PC problems and the intensity of PC input. CONCLUSIONS: Large-scale clinical data supports the use of a Pareto-based quantitative framework for a workforce comprising of mainly generalist PC staff supported by smaller numbers of PC specialists.

SNP web resources and their potential applications in personalized medicine.

Single nucleotide polymorphisms (SNPs) are the commonest genetic variant in the human genome and have been associated with inter-individual differences in drug response. Finding the causative SNPs underlying variations in drug response has been a cornerstone of personalized medicine. However, as there are over 19 million SNPs, the task of finding causative SNPs underlying differences in drug response using in vitro and in vivo methods can be intimidating. SNP related web resources can be invaluable in the search for SNPs relevant to drug response phenotypes as they represent relatively cheaper yet efficient ways of prioritizing relevant SNPs for further study. These resources serve as repositories of SNP information or contain in silico tools that can predict the functionality of a SNP. More sophisticated resources integrate the information repository function with the predictive function to create a one stop SNP resource for researchers. SNP related web resources can also aid researchers in planning and analyzing different types of genetic association studies by aiding in selecting SNPs for genotyping in these studies. The focus of this mini review is to outline the SNP related web resources that are available to researchers and how these resources may aid researchers studying SNP-drug response phenotype associations. Through efficient utilization of SNP related web resources, researchers will hopefully be able accelerate the pace of SNP related research in pharmacogenomics by identifying high risk SNP variants contributing to drug response as well as developing novel therapeutic targets based on understanding how SNPs alter drug response pathways.

A non-synonymous single nucleotide polymorphism in an OPRM1 splice variant is associated with fentanyl-induced emesis in women undergoing minor gynaecological surgery.

BACKGROUND: Fentanyl-induced emesis (FIE) is a distressing adverse effect in the postoperative setting. The genetic basis of FIE remains largely unknown, therefore, we examined whether it was associated with specific genetic variants of OPRM1, the gene encoding the main receptor target of fentanyl. METHODS: In this prospective case-control study, 193 women undergoing gynaecological surgery under a standardized anaesthetic with a low emetogenic risk were enrolled. Inclusion and exclusion criteria were designed to select extreme phenotypes as well as to ensure that most major confounders for FIE were either excluded or present in all patients. To control for unforeseen intra- and postoperative confounders for FIE, only 161 patients were further analysed, out of which 10 were categorized as having FIE, defined by the presence of at least one of three symptoms: nausea, vomiting or retching that was likely to be fentanyl-related. To identify SNPs relevant to FIE in our population, DNA from 40 controls and 10 cases was sequenced at the following OPRM1 regions: 3 kbp of the promoter, main and alternative exons as well as 2 kbp of the 3' downstream region. The genotype of the significant SNP was further determined in the remaining 111 controls. RESULTS: The incidence of FIE was 6.2%. Initial sequencing of 10 cases and 40 controls identified 25 SNPs. Only rs540825, a non-synonymous SNP in the splice variant, MOR1X, showed a significant association with FIE post-Bonferroni correction. This SNP was further examined in the remaining 111 controls which confirmed its significant association with FIE (p = 0.019 post-Bonferroni, OR: 5.6, 95% CI: 1.42-21.91). CONCLUSIONS: This is the first report of an association between the occurrence of FIE in Chinese women undergoing gynaecological surgery and an OPRM1 splice variant SNP, rs540825.

Predicting potentially functional SNPs in drug-response genes.

SNPs are known to contribute to variations in drug response and there are more than 14 million polymorphisms spanning the human genome. However, not all of these SNPs are functional. It would be impractical and costly to evaluate every individual SNP for functionality experimentally. Consequently, one of the major challenges for researchers has been to seek out functional SNPs from all the SNPs in the human genome. In silico or bioinformatic methods are economical, less labor intensive, yet powerful approaches to filter out potentially functional SNPs in drug-response genes for further study. This allows researchers to prioritize which SNPs to subsequently evaluate experimentally for drug-response studies, as well as potentially providing insights into possible mechanisms underlying how SNPs may affect drug-response genes.

The G allele of SNP E1/A118G at the mu-opioid receptor gene locus shows genomic evidence of recent positive selection.

Opioid drug response and pain perception differs greatly amongst different individuals. The micro-opioid receptor (MOR) is the main receptor target for important opioid analgesics. As SNPs may contribute to interindividual differences in drug response, in silico signatures of recent positive selection (RPS) were utilized to seek out potentially functional SNPs in the MOR gene in order to facilitate the prioritization of SNPs for evaluation in genetic association studies. Out of over 1000 SNPs at the MOR locus, 184 high-frequency SNPs were interrogated for signatures of RPS. A total of five SNPs (four noncoding and one nonsynonymous coding) demonstrated in silico evidence of RPS. Significantly, the nonsynonymous E1/A118G SNP, which was previously reported to be functionally important, showed in silico evidence of RPS. This reaffirms the feasibility of utilizing in silico signatures of RPS to identify potentially functionally significant SNPs for association studies. Interestingly, the positively selected G allele of this RPS SNP was also predicted to create a novel exon splice enhancer as well as p53 binding sites.

The Singaporean English and Chinese versions of the EQ-5D achieved measurement equivalence in cancer patients.

OBJECTIVE: To assess measurement equivalence of the Singaporean English and Chinese versions of the EuroQol Group's 5-domain questionnaire (EQ-5D) in cancer patients. STUDY DESIGN AND SETTING: Seven hundred and seventy-one ethnic Chinese patients in Singapore were recruited, and they answered either an English or a Chinese version of the EQ-5D. Seven days later, a similar questionnaire in the same language was mailed to the patients. Regression analysis was used to assess equivalence of the mean values obtained by using the two language versions. The validity, responsiveness to change, and reliability of the two versions of the EQ-5D were assessed and compared. RESULTS: Based on the prespecified equivalence margin of +/-10% for binary outcome, +/-0.05 for utility index, and +/-5 points in the visual analog scale, the two language versions of the EQ-5D gave equivalent mean values at item and scale levels. They also showed similar characteristics in validity, responsiveness, and reliability. For example, the test-retest reliability values for the EQ-5D utility index in the two language samples were identical in two significant digits: 0.79. CONCLUSION: The Singaporean English and Chinese versions of the EQ-5D were validated in cancer patients and were shown to achieve measurement equivalence.