Technological readiness and implementation of genomic-driven precision medicine for complex diseases.

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.

Social position and geriatric syndromes among Swedish older people: a population-based study.

BACKGROUND: Older people with a low social position are at higher risk of poor health outcomes compared to those with a higher social position. Whether lower social position also increases the risk of geriatric syndromes (GSs) remains to be determined. This study investigates the association of social position with GSs among older community-dwellers. METHODS: Three consecutive population-based health surveys in 2006, 2010 and 2014 among older community-dwellers (age 65-84 years) in Stockholm County were combined (n = 17,612) and linked with Swedish administrative registry information. Social position was assessed using registry information (i.e. education, country of origin and civil status) and by self-reports (i.e. type of housing and financial stress). GSs were assessed by self-reports of the following conditions: insomnia, urinary incontinence, functional decline, falls, depressive disorder, hearing or vision problems. Binomial logistic regression analyses were used to estimate the association between social position and GSs after adjusting for age, sex, health status, health behavior and social stress. RESULTS: The prevalence of GSs was 70.0%, but varied across GSs and ranged from 1.9% for depression to 39.1% for insomnia. Living in rented accommodation, being born outside the Nordic countries, being widowed or divorced were associated with GS presence. Financial stress was most strongly associated with GSs (adjusted odds ratio, 2.59; 95% CI, 2.13-3.15). CONCLUSION: GSs are highly prevalent among older Swedish community-dwellers with wide variations across syndromes and strong association with all measures of social position, most strikingly that of experiencing financial stress.

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus.

The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease-oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow-up: strategies in care planning, self-management and medication-related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self-management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.

Antidepressants and mortality risk in a dementia cohort: data from SveDem, the Swedish Dementia Registry.

BACKGROUND: The association between mortality risk and use of antidepressants in people with dementia is unknown. OBJECTIVE: To describe the use of antidepressants in people with different dementia diagnoses and to explore mortality risk associated with use of antidepressants 3 years before a dementia diagnosis. METHODS: Study population included 20 050 memory clinic patients from the Swedish Dementia Registry (SveDem) diagnosed with incident dementia. Data on antidepressants dispensed at the time of dementia diagnosis and during 3-year period before dementia diagnosis were obtained from the Swedish Prescribed Drug Register. Cox regression models were used. RESULTS: During a median follow-up of 2 years from dementia diagnosis, 25.8% of dementia patients died. A quarter (25.0%) of patients were on antidepressants at the time of dementia diagnosis, while 21.6% used antidepressants at some point during a 3-year period before a dementia diagnosis. Use of antidepressant treatment for 3 consecutive years before a dementia diagnosis was associated with a lower mortality risk for all dementia disorders and in Alzheimer's disease. CONCLUSION: Antidepressant treatment is common among patients with dementia. Use of antidepressants during prodromal stages may reduce mortality in dementia and specifically in Alzheimer's disease.

Educational disparities in antipsychotic drug use among older people with and without dementia in Sweden.

OBJECTIVE: Antipsychotic drugs are commonly used to treat behavioural and psychological symptoms of dementia. The aim was to investigate if socioeconomic position was associated with antipsychotic drug treatment among older adults with and without dementia. METHOD: By record linkage of the Swedish Prescribed Drug Register, Patient Register, and Educational Register, we obtained information on antipsychotics, dementia status, and educational level for 641,566 persons aged 75-89 year old in Sweden 2005. RESULTS: Among persons diagnosed with dementia (n = 32 092), 21% used antipsychotics compared with 4% in the total sample (n = 641,566). Lower education was associated with a higher probability of antipsychotic use in the total sample (adjusted odds ratio [OR] low vs. high education: 1.56; 95% confidence interval [CI]: 1.48-1.64). In the dementia subpopulation, lower education was also associated with a higher likelihood of use of antipsychotics (adjusted OR(low vs. high) 1.43; 95% CI: 1.28-1.59). CONCLUSION: People with dementia were five times more likely to use antipsychotic drugs than the general population of older adults. Also, lower education was associated with a higher use of antipsychotics, both in the general population and in the subgroup of persons with dementia. This finding highlights the importance of investigating healthcare inequalities also among cognitively impaired older adults.

Educational level and use of osteoporosis drugs in elderly men and women: a Swedish nationwide register-based study.

SUMMARY: We examined educational disparities in use of osteoporosis drugs in a nationwide population of Swedes aged 75-89 years old. Individuals with high education were more likely to receive osteoporosis drug treatment than lower educated individuals, particularly among women. INTRODUCTION: This study aims to investigate whether educational level is associated with use of osteoporosis drugs in the general population of older men and women in Sweden, also after adjustment for fractures. METHODS: By record linkage of The Swedish Prescribed Drug Register, The Swedish Patient Register, and The Swedish Education Register, we obtained information on filling of prescriptions for osteoporosis drugs (bisphosphonates, calcium/vitamin D combinations, and selective estrogen receptor modulators) from July to October 2005, osteoporotic fractures from 1998 to 2004, and educational level for 645,429 people aged 75-89 years. Multivariate logistic regression analysis was used to investigate whether education was associated with use of osteoporosis drug therapy. RESULTS: Higher education was associated with use of osteoporosis drugs for both men [odds ratio (OR)(high education vs low), 1.27; 95% confidence interval (CI), 1.19-1.35] and women (OR(high education vs low), 1.57; 95% CI, 1.52-1.61), after adjustment for age, osteoporotic fractures, and comorbidity (i.e., number of other drugs). Among those who had sustained a fracture (n = 57,613), the educational differences in osteoporosis drug treatment were more pronounced in women than men. Further, women were more likely to receive osteoporosis drug treatment after osteoporotic fracture. CONCLUSION: Uptake of osteoporosis drug therapy seems to be unequally distributed in the elderly population, even in a country with presumably equal access to health care.

Undertreatment of osteoporosis in persons with dementia? A population-based study.

UNLABELLED: In this population-based study of more than 2,600 elderly, people with dementia received less preventive treatment for osteoporosis compared to people without dementia, although osteoporotic fractures were more common in patients with dementia. Thus, our results indicate an undertreatment of osteoporosis in dementia. INTRODUCTION: This study compares the use of osteoporosis drugs in elderly with and without dementia, taking into account osteoporotic fractures and type of housing. METHODS: We analyzed data from the baseline examination (2001-2004) of The Swedish National Study on Aging and Care- Kungsholmen (SNAC-K), Stockholm, Sweden. Participants were aged ≥ 66 years (n = 2610). We analysed the use of bisphosphonates, raloxifene, and calcium/vitamin D combinations in relation to clinically based dementia diagnosis. Information about osteoporotic fractures during the previous 4 years was obtained from the Swedish National Patient Register. We used logistic regression to analyze the association between dementia status and use of osteoporosis drugs. RESULTS: Osteoporosis drugs (mainly calcium/vitamin D combinations) were used by 5% of the persons with dementia and 12% of the persons without dementia. Furthermore, 25% of the persons with dementia and 7% of the persons without dementia had had at least one osteoporotic fracture during the past 4 years. After controlling for age, sex, osteoporotic fractures, and type of housing (own home or institution), persons with dementia were less likely to use osteoporosis drugs than persons without dementia (OR = 0.34; 95% CI, 0.19-0.59). CONCLUSIONS: Our results indicate an undertreatment of osteoporosis in persons with dementia, although osteoporotic fractures are common among these patients.

Trends in polypharmacy and potential drug-drug interactions across educational groups in elderly patients in Sweden for the period 1992 - 2002.

OBJECTIVE: This study investigates the changes in drug use, polypharmacy and potential drug-drug interactions (DDIs) between educational groups of Swedish elderly over a 10-year period from 1992 - 2002. METHODS: We used data from SWEOLD I (n = 512) from 1992 and SWEOLD II from 2002 (n = 561), which are nationally representative surveys of the elderly population in Sweden aged 77 years and older. Both community-based and institutionalized persons were included. Information on drug use was based on personal interviews and all drugs used in the two weeks prior to the studies were recorded. The three outcomes under study were drug use, polypharmacy (concurrent use of five or more drugs), and potential DDIs. RESULTS: In the SWEOLD data from 1992 - 2002, the mean number of drugs used per person increased from 2.5 - 4.4. Overall, 81% of the study participants were drug users in 1992 as compared to 88% in 2002. The prevalence of polypharmacy increased 3-fold (from 18% in 1992 to 42% in 2002) after controlling for age and gender. In both SWEOLD surveys, the less educated reported polypharmacy more often (19% in 1992 and 46% in 2002) than the higher educated (12% in 1992 and 36% in 2002). Potential DDIs also increased, both among the less educated (14% in 1992 to 26% in 2002) and the higher educated (18% in 1992 to 24% in 2002). The most pronounced changes in the consumption of specific drug groups were observed in antithrombotic agents, beta-blocking agents, ACE inhibitors, and vitamin B12 and folic acid. In general, the use of most therapeutic classes increased more among the well educated compared to less educated men between 1992 and 2002, whereas the opposite relationship prevailed among women. CONCLUSION: This study indicates that the use of drugs, polypharmacy and potential DDIs have increased during 1992 to 2002 among the elderly. These changes were most prominent among the less educated women. Polypharmacy and potential DDIs represent potential health hazards for the elderly. Therefore, the trends of increasing polypharmacy and drug-drug interactions deserve attention and the mechanisms behind should be investigated further.

Neighbourhood social participation and women's use of anxiolytic-hypnotic drugs: a multilevel analysis.

STUDY OBJECTIVES: To identify and quantify a hypothesised collective effect of the neighbourhood on individual use of anxiolytic-hypnotic drugs (AHD). To analyse the general impact of neighbourhood social participation on use of AHD, adjusting for individual characteristics. DESIGN: Cross sectional analysis performed by multilevel logistic regression with women at the first level and neighbourhoods at the second level. SETTING: Malmö (250 000 inhabitants), Sweden. PARTICIPANTS: 15 456 women aged 45 to 73, residing in 95 neighbourhoods in Malmö, who took part in the Malmö diet and cancer study (1991-1996). MAIN RESULTS: The prevalence of AHD use was 5.5% in the study sample. Overall, 1.7% of the total individual differences in the propensity for using AHD were explained by the neighbourhood level. This percentage, however, differed between different individuals. Low level of social participation in the neighbourhood was associated with higher probability of AHD use (OR = 3.10 (95% CI 1.51 to 6.41)), independently of individual age, low social participation, low educational level, and living alone. This association was reduced (OR = 2.01 (95% CI 0.97 to 4.14)) after the additional accounting for individual disability pension, low self rated health, stress, and medication for somatic disorders. CONCLUSIONS: The neighbourhood level of social participation seems to affect individual use of AHD, possibly through individual characteristics. However, neighbourhood boundaries play a minor part in understanding individual AHD use in the city of Malmö.