First ever characterisation of the effects of short telomeres in a Singapore interstitial lung disease cohort.

BACKGROUND: Differences in disease behaviour and genotypes are described in Asian and Western interstitial lung disease (ILD) cohorts. Short leukocyte telomere length (LTL) correlates with poor outcomes in Western ILD cohorts but its significance in Asian populations is unknown. We aim to characterise the burden and clinical implications of short LTL in Singaporean ILD patients. METHODS: Patients diagnosed with ILD at Singapore General Hospital were prospectively recruited and compared against 36 healthy controls. The primary outcome was transplant-free survival. Genomic DNA from peripheral blood was extracted and LTL measured using quantitative polymerase chain reaction assay (qPCR). RESULTS: Amongst 165 patients, 37% had short LTL. There was a higher proportion of combined pulmonary fibrosis and emphysema (CPFE) patients with short LTL (n = 21, 34.4% vs n = 16, 15.4%; p < 0.001). Short LTL patients had reduced survival at 12-, 24- and 36-months and median survival of 24 months (p < 0.001) which remained significant following adjustment for smoking, GAP Stage and radiological UIP pattern (Hazard Ratio (HR), 2.74; 95%CI:1.46, 5.11; p = 0.002). They had increased respiratory-related mortality and acute exacerbation incidences. Despite similar baseline lung function, short LTL patients had a faster decline in absolute forced vital capacity (FVC) of -105.3 (95% CI: 151.4, -59.1) mL/year compared to -58.2 (95% CI: 82.9, -33.6) mL/year (p < 0.001) in normal LTL patients. CONCLUSION: Short LTL correlated with increased mortality and faster lung function decline in our Singaporean ILD cohort with a magnitude similar to that in Western ILD cohorts. Further research is needed to integrate LTL assessment into clinical practice.

Using the Actor-Partner Interdependence Model to explore the psychological impact of COVID-19 on anxiety in dyads of patients with cancer and caregivers.

BACKGROUND: Delineating the compound psychological effect of the pandemic on cancer care, and the interdependency across cancer patient-caregiver dyads have yet to be explored. This study examines the levels of psychological impact of COVID-19 on patient-caregiver dyads anxiety, and the interdependent associations between their COVID-19 and cancer concerns, and risk perceptions. METHOD: There were 352 patients and caregivers (patient-caregiver dyads, N = 176) included in this study (43.2% spousal dyads). Generalized Anxiety Disorder-7 and questionnaires regarding risk perception, perceived confidence in healthcare system, COVID-19, and cancer-related concerns were administered. Actor-Partner Interdependence Model (APIM) analyses were used to determine the interdependent effects. Indirect effects were tested using mediation pathway analyses. RESULTS: Patients reported significantly higher levels of risk perceptions and anxiety than their caregivers (p < 0.01). Anxiety rates (GAD-7 ≥ 10) were also significantly higher (26.7% vs 18.2%, p < 0.01). Dyads' anxiety, "general COVID-19 concerns," "cancer-related concerns," and risk perceptions were correlated (ps < 0.01). APIM showed only actor effects of general COVID-19 concerns, cancer-related COVID-19 concerns, and risk perceptions on anxiety (ßs = 0.19-0.53, ps < 0.01). No partner effects were observed. Similar results were found in the composite APIM. Indirect effects of the patient/caregiver's variables on their partner's anxiety were observed in the mediation analyses. CONCLUSION: Concerns about COVID-19 and cancer care could be indirectly associated in patient-caregiver dyads and need to be proactively addressed. As pandemic evolves into endemicity, engagement with patients and caregivers should strive to be sensitive to their differential needs and messages should be tailored to the informational needs of each.

Geographical, ethnic, and genetic differences in pancreatic cancer predisposition.

Pancreatic cancer remains a leading cause of cancer-related mortality worldwide. Treatment outcomes remain largely dismal despite significant medical advancements. This lends urgency to the need to understand its risk factors in order to guide early detection and improve outcomes. There are both modifiable and non-modifiable risk factors, the more established of such being that of age, smoking, obesity, diabetes mellitus (DM), alcohol and certain genetic predisposition syndromes with underlying germline mutations. Some genetic predisposition syndromes such as BRCA1/2, PALB2, ATM, and CDKN2A are well-established, arising from germline mutations that result in carcinogenesis through mechanisms such as cell injury, dysregulation of cell growth, dysfunctional DNA repair, and disruption of cell mobility and adhesion. There is also a significant proportion of familial pancreatic cancer (FPC) for which the underlying predisposing genetic mechanism is not yet understood. Nuances have emerged in the ethnic and geographical differences of pancreatic cancer predisposition, and these may be attributed to differences in lifestyle, standard of living, socioeconomic factors, and genetics. This review describes in detail the factors contributing to pancreatic cancer with focus on ethnic and geographical differences and hereditary genetic syndromes. Greater insight into the interplay of these factors can guide clinicians and healthcare authorities in addressing modifiable risk factors, implementing measures for early detection in high-risk individuals, initiating early treatment of pancreatic cancer, and directing future research towards existing knowledge deficits, in order to improve survival outcomes.

General practitioners' (GPs) experience, attitudes and needs on clinical genetic services: a systematic review.

OBJECTIVE: The proliferation and growing demands of genetic testing are anticipated to revolutionise medical practice. As gatekeepers of healthcare systems, general practitioners (GPs) are expected to play a critical role in the provision of clinical genetic services. This paper aims to review existing literature on GPs' experience, attitudes and needs towards clinical genetic services. DESIGN: A systematic mixed studies review of papers published between 2010 and 2022. ELIGIBILITY CRITERIA: The inclusion criterion was peer-reviewed articles in English and related to GPs' experience, views and needs on any genetic testing. INFORMATION SOURCES: The PubMed, PsycINFO, Cochrane, EMBASE databases were searched using Mesh terms, Boolean and wildcards combinations to identify peer-reviewed articles published from 2010 to 2022. Study quality was assessed using Mixed Methods Appraisal Tool. Only articles that fulfilled the inclusion criteria were selected. A thematic meta-synthesis was conducted on the final sample of selected articles to identify key themes. RESULTS: A total of 62 articles were included in the review. Uncertainty over GPs' role in providing genetic services were attributed by the lack of confidence and time constraints and rarity of cases may further exacerbate their reluctance to shoulder an expanded role in clinical genetics. Although educational interventions were found to increasing GPs' knowledge and confidence to carry out genetic tasks, varied interest on genetic testing and preference for a shared care model with other genetic health professionals have resulted in minimal translation to clinical adoption. CONCLUSION: This review highlights the need for deeper exploration of GPs' varied experience and attitudes towards clinical genetic services to better facilitate targeted intervention in the adoption of clinical genetics.

How practice setting affects family physicians' views on genetic screening: a qualitative study.

BACKGROUND: Genetic screening (GS), defined as the clinical testing of a population to identify asymptomatic individuals with the aim of providing those identified as high risk with prevention, early treatment, or reproductive options. Genetic screening (GS) improves patient outcomes and is accessible to the community. Family physicians (FPs) are ideally placed to offer GS. There is a need for FPs to adopt GS to address anticipated genetic specialist shortages. OBJECTIVE: To explore FP attitudes, perceived roles, motivators and barriers, towards GS; and explore similarities and differences between private and public sector FPs. METHODS: We developed a semi-structured interview guide using existing literature. We interviewed private and public sector FPs recruited by purposive, convenience and snowballing strategies, by telephone or video to theme saturation. All sessions were audio-recorded, transcribed and coded for themes by two independent researchers with an adjudicator. RESULTS: Thirty FPs were interviewed (15 private, 15 public). Theme saturation was reached for each group. A total of 12 themes (6 common, 3 from private-practice participants, 3 public-employed participants) emerged. Six common major themes emerged: personal lack of training and experience, roles and relevance of GS to family medicine, reluctance and resistance to adding GS to practice, FP motivations for adoption, patient factors as barrier, and potential solutions. Three themes (all facilitators) were unique to the private group: strong rapport with patients, high practice autonomy, and high patient literacy. Three themes (all barriers) were unique to the public group: lack of control, patients' lower socioeconomic status, and rigid administrative infrastructure. CONCLUSION: FPs are motivated to incorporate GS but need support for implementation. Policy-makers should consider the practice setting when introducing new screening functions. Strategies to change FP behaviours should be sensitive to their sense of autonomy, and the external factors (either as facilitators or as barriers) shaping FP practices in a given clinical setting.

Effects of housing value and medical subsidy on treatment and outcomes of breast cancer patients in Singapore: A retrospective cohort study.

BACKGROUND: Socioeconomic status (SES) is likely to affect survival in breast cancer patients. Housing value is a reasonable surrogate for SES in Singapore where most residents own their own homes, which could be public (subsidised) or private housing. We evaluated effects of housing value and enhanced medical subsidies on patients' presentation, treatment choices, compliance and survival in a setting of good access to healthcare. METHODS: A retrospective analysis of breast cancer patients treated in a tertiary hospital cluster from 2000 to 2016 was performed. Individual-level Housing value Index (HI) was derived from each patient's address and then grouped into 3 tiers: HI(high)(minimal subsidy), HI(med)(medium subsidy) and HI(low)(high subsidy). Cox regression was performed to evaluate the associations between overall survival (OS) and cancer-specific survival (CSS) with HI and various factors. FINDINGS: We studied a multiracial cohort of 15,532 Stage 0-IV breast cancer patients. Median age was 53.7 years and median follow-up was 7.7 years. Patients with lower HI presented with more advanced disease and had lower treatment compliance. On multivariable analysis, compared to HI(high) patients, HI(med) patients had decreased OS (HR=1.14, 95% CI 1.05-1.23) and CSS (HR=1.15, 95% CI 1.03-1.27), and HI(low) patients demonstrated reduced OS (HR=1.16, 95% CI 1.01-1.33). Ten-year non-cancer mortality was higher in lower HI-strata. Enhanced medical subsidy approximately halved treatment noncompliance rates but its receipt was not an independent prognostic factor for survival. INTERPRETATION: Despite good healthcare access, lower-HI patients have poorer survival from both cancer and non-cancer causes, possibly due to delayed health-seeking and poorer treatment compliance. Enhanced subsidies may mitigate socioeconomic disadvantages. FUNDING: None.

Managing cancer in context of pandemic: a qualitative study to explore the emotional and behavioural responses of patients with cancer and their caregivers to COVID-19.

OBJECTIVES: Having to access life-sustaining treatment during the emerging COVID-19 outbreak has placed patients with cancer at an especially vulnerable position notwithstanding their immunocompromised condition. The present study aimed to elucidate cancer patients' and their caregivers' experiences during this outbreak. DESIGN: Face-to-face semistructured interviews were conducted. SETTING: A tertiary cancer care facility. PARTICIPANTS: 16 patients with cancer and 14 caregivers. Inclusions criteria were: (A) diagnosed with cancer, (B) receiving active treatment or follow-ups, (C) aged 21 years and above and (D) fluent in English or Mandarin. RESULTS: Thematic analysis was conducted. Five themes were identified: heightened sense of threat, impact on healthcare experience, responsibility falls on oneself, striving for normalcy and sense of safety and trust. Heightened threat of COVID-19 was more pronounced in patients and linked to vulnerability and fear, uncertainty and actions of socially irresponsible others. Dominant in their healthcare experience was prioritising cancer and treatment amidst heightened threat and anticipatory worry about treatment disruptions. Both noted on the importance of taking responsibility for one's health, with caregivers reporting a reinforced sense of duty towards patients. They strived to maintain normalcy by viewing COVID-19 as beyond personal control, downplaying and living life as usual. Their resolve was supported by a sense of safety from the actions of authorities, hospitals and trust towards healthcare providers. CONCLUSIONS: Cancer intensifies threat and the emotional impact of COVID-19 and may trigger specific concerns related to treatment. Psychoeducation interventions led by healthcare providers over digital platforms could help address cancer-specific concerns and support patients and caregivers during the pandemic.

Use of telephone intake for family history taking at a cancer genetics service in Asia.

Family history taking is a fundamental part of genetic counseling, and however, it is also a time-consuming process. To cope with the increasing demands at the Cancer Genetics Service in Singapore, alternative methods to collect patients' family history were implemented to reduce the duration of the initial consultation and increase the clinic's capacity. Two interventions were performed in this study, where a family history questionnaire and telephone intakes (telephone calls to collect patient family history) were implemented prior to a cancer genetics consultation. The primary outcome of this study is the duration of the initial consultation in relation to both interventions while the secondary outcome is the clinic attendance rate before and after implementing the telephone intake. The impact of interventions was evaluated with a Plan-Do-Study-Act (PDSA) methodology. The use of a family history questionnaire could not be evaluated due to poor patient response while the telephone intake was found to be feasible among the local population. Two improvements were observed after the implementation of telephone intake: (a) a significant reduction in the duration of the initial consultation from 60 to 45 min (p = .001) and (b) a significant increase of 29.7% in clinic attendance (p = .01). This study demonstrates that collecting family history information ahead of genetic counseling via telephone intake is a useful measure in improving clinic capacity, which potentially resulting in optimization of clinical resources.