Measuring Multimorbidity

Multimorbidity is common. The gaps in multimorbidity research are in the measurement of the prevalence, the levels of multimorbidity and its associated outcomes. This thesis aimed to provide a uniform definition for multimorbidity, identify instruments for measuring the level of multimorbidity, and describe patient-reported outcomes for different levels of multimorbidity. Three studies were conducted. The first determined the prevalence rates of multimorbidity and explored whether there were differences among the different age, gender and ethnic groups in the primary care population. Common dyads and triads of conditions were described. The systematic review updated the list of instruments for measuring the level of multimorbidity for community-dwelling adults. The third study determined the association of different levels of multimorbidity with depression, anxiety and quality of life. The agreement between patients’ self-reported conditions and conditions recorded in their electronic medical records (EMR) were reported. Increasing age was associated with a higher prevalence of multimorbidity. The commonest dyad was hyperlipidaemia/hypertension, and triad was hyperlipidaemia/hypertension/diabetes. Disease count and weighted indices were the most commonly used instruments for measuring the level of multimorbidity. Self-reported disease count was positively associated with depression and anxiety, and negatively associated with quality of life. Stroke was the only condition that showed substantial agreement between patients’ self-reported medical conditions and the EMR. We identified a practical definition of multimorbidity in the Singapore primary care population, described the commonly used instruments for measuring the level of multimorbidity, and reported the disparity of multimorbidity outcomes between patients’ self-reported chronic conditions and EMR

Advancing cross-national planning and partnership: proceedings from the International Multimorbidity Symposium 2019

The International Multimorbidity Symposium was held in November 2019 at Western University to achieve three main objectives: to discuss progress and findings from various jurisdictions; to facilitate collaboration through group discussion to identify strategies to move multimorbidity research forward; and to create concrete plans to ensure advances in multimorbidity research and knowledge can be achieved through cross-national partnership. This event included keynote presentations, elevator pitch presentations and breakout sessions and there was a total of 35 attendees from eight countries, representing diverse disciplines and training levels. The overall themes arising from the event were: the importance of integrating the study and management of multimorbidity from both the primary care and public health perspectives; meaningful engagement and collaboration with patients and caregivers to understand key dimensions of multimorbidity; the considerable benefit of collaborative international partnerships; and the need to spread and scale innovations for health care systems that can better respond to the complex needs of patients and caregivers who are living with multimorbidity. Finally, it was well-acknowledged among the attendees that expanding the collaboration and discussion among international colleagues via in-person and virtual events will be important to move multimorbidity research forward

Hormone Therapy and the Risk of Breast Cancer in BRCA1 Mutation Carriers

Background: Hormone therapy (HT) is commonly given to women to alleviate the climacteric symptoms associated with menopause. There is concern that this treatment may increase the risk of breast cancer. The potential association of HT and breast cancer risk is of particular interest to women who carry a mutation in BRCA1 because they face a high lifetime risk of breast cancer and because many of these women take HT after undergoing prophylactic surgical oophorectomy at a young age. Methods: We conducted a matched case-control study of 472 postmenopausal women with a BRCA1 mutation to examine whether or not the use of HT is associated with subsequent risk of breast cancer. Breast cancer case patients and control subjects were matched with respect to age, age at menopause, and type of menopause (surgical or natural). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with conditional logistic regression. Statistical tests were two-sided. Results: In this group of BRCA1 mutation carriers, the adjusted OR for breast cancer associated with ever use of HT compared with never use was 0.58 (95% CI = 0.35 to 0.96; P =. 03). In analyses by type of HT, an inverse association with breast cancer risk was observed with use of estrogen only (OR = 0.51, 95% CI = 0.27 to 0.98; P =. 04); the association with use of estrogen plus progesterone was not statistically significant (OR = 0.66, 95% CI = 0.34 to 1.27; P =. 21). Conclusion: Among postmenopausal women with a BRCA1 mutation, HT use was not associated with increased risk of breast cancer; indeed, in this population, it was associated with a decreased risk

Advancing cross-national planning and partnership: Proceedings from the International Multimorbidity Symposium 2019.

The International Multimorbidity Symposium was held in November 2019 at Western University to achieve three main objectives: to discuss progress and findings from various jurisdictions; to facilitate collaboration through group discussion to identify strategies to move multimorbidity research forward; and to create concrete plans to ensure advances in multimorbidity research and knowledge can be achieved through cross-national partnership. This event included keynote presentations, elevator pitch presentations and breakout sessions and there was a total of 35 attendees from eight countries, representing diverse disciplines and training levels. The overall themes arising from the event were: the importance of integrating the study and management of multimorbidity from both the primary care and public health perspectives; meaningful engagement and collaboration with patients and caregivers to understand key dimensions of multimorbidity; the considerable benefit of collaborative international partnerships; and the need to spread and scale innovations for health care systems that can better respond to the complex needs of patients and caregivers who are living with multimorbidity. Finally, it was well-acknowledged among the attendees that expanding the collaboration and discussion among international colleagues via in-person and virtual events will be important to move multimorbidity research forward.status: Published onlin

Analysis of clinically relevant variants from ancestrally diverse Asian genomes.

10.1038/s41467-022-34116-9Nat Commun1316694

Turnovers and Housing Price Dynamics: Evidence from Singapore Condominium Market

10.1007/s11146-008-9155-xJournal of Real Estate Finance and Economics383254-27

Young age at first pregnancy does protect against early onset breast cancer in BRCA1 and BRCA2 mutation carriers

Background: Previous research assessing the impact of pregnancy and age at first pregnancy on breast cancer risk in BRCA1 and BRCA2 mutation carriers has produced conflicting results, with some studies showing an increased risk following early first pregnancy in contrast to the reduced risk in the general population of women. Methods: Female BRCA1 and BRCA2 carriers from North West England were assessed for breast cancer incidence prior to 50 years of age comparing those with an early first full-term pregnancy (<21 years) to those without a full-term pregnancy. Breast cancer incidence per decade from 20 years and Kaplan-Meier analyses were performed. Results: 2424 female mutation carriers (1278 BRCA1; 1146 BRCA2) developed 990 breast cancers under the age of 50 years. Women who had their first term pregnancy prior to age 21 (n=441) had a lower cancer incidence especially between age 30-39 years. Kaplan-Meier analysis showed an odds ratio of 0.78 for BRCA1 (p=0.005) and 0.73 for BRCA2 (p=0.002). Conclusions: The present study demonstrates a clear protective effect of early first pregnancy on breast cancer risk in both BRCA1 and BRCA2 mutation carriers

Analysis of clinically relevant variants from ancestrally diverse Asian genomes

Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture. About 27% of severe recessive disorder genes with appreciable carrier frequencies in Asians are missed by carrier screening panels, and we estimate 0.5% Asian couples at-risk of having an affected child. Prevalence of medically-actionable variant carriers is 3.4% and a further 1.6% harbour variants with potential for pathogenic classification upon additional clinical/experimental evidence. We profile 23 pharmacogenes with high-confidence gene-drug associations and find 22.4% of Asians at-risk of Centers for Disease Control and Prevention Tier 1 genetic conditions concurrently harbour pharmacogenetic variants with actionable phenotypes, highlighting the benefits of pre-emptive pharmacogenomics. Our findings illuminate the diversity in genetic disease epidemiology and opportunities for precision medicine for a large, diverse Asian population.</p