An inventory of collaborative medication reviews for older adults-evolution of practices

Background Collaborative medication review (CMR) practices for older adults are evolving in many countries. Development has been under way in Finland for over a decade, but no inventory of evolved practices has been conducted. The aim of this study was to identify and describe CMR practices in Finland after 10 years of developement. Methods An inventory of CMR practices was conducted using a snowballing approach and an open call in the Finnish Medicines Agency's website in 2015. Data were quantitatively analysed using descriptive statistics and qualitatively by inductive thematic content analysis. Clyne et al's medication review typology was applied for evaluating comprehensiveness of the practices. Results In total, 43 practices were identified, of which 22 (51%) were designed for older adults in primary care. The majority (n = 30, 70%) of the practices were clinical CMRs, with 18 (42%) of them being in routine use. A checklist with criteria was used in 19 (44%) of the practices to identify patients with polypharmacy (n = 6), falls (n = 5), and renal dysfunction (n = 5) as the most common criteria for CMR. Patients were involved in 32 (74%) of the practices, mostly as a source of information via interview (n = 27, 63%). A medication care plan was discussed with the patient in 17 practices (40%), and it was established systematically as usual care to all or selected patient groups in 11 (26%) of the practices. All or selected patients' medication lists were reconciled in 15 practices (35%). Nearly half of the practices (n = 19, 44%) lacked explicit methods for following up effects of medication changes. When reported, the effects were followed up as a routine control (n = 9, 21%) or in a follow-up appointment (n = 6, 14%). Conclusions Different MRs in varying settings were available and in routine use, the majority being comprehensive CMRs designed for primary outpatient care and for older adults. Even though practices might benefit from national standardization, flexibility in their customization according to context, medical and patient needs, and available resources is important.Peer reviewe

Community Pharmacists' Contribution to Medication Reviews for Older Adults : A Systematic Review

ObjectivesTo identify medication review interventions for older adults that involve community pharmacists and evidence of outcomes of these interventions. DesignSystematic review. MeasurementsCinahl, MEDLINE (Ovid), Scopus, International Pharmaceutical Abstracts, and Cochrane Library were searched for articles published between January 2000 and February 2016. Articles involving community pharmacists in medication reviews for outpatients aged 65 and older were included. Evidence of economic, clinical, and humanistic outcomes of interventions was summarized. ResultsSixteen articles were found that described 12 medication review interventions, of which 6 were compliance and concordance reviews, 4 were clinical medication reviews, and 2 were prescription reviews according to a previously developed typology. Community pharmacists' contributions to reviewing medications varied from sending the dispensing history to other healthcare providers to comprehensive involvement in medication management. The most commonly assessed outcomes of the interventions were medication changes leading to reduction in actual or potential drug-related problems (n=12) and improved adherence (n=5). ConclusionRegardless of community pharmacists' contributions to interventions, medication review interventions seem to reduce drug-related problems and increase medication adherence. More well-designed, rigorous studies with more sensitive and specific outcomes measures need to be conducted to assess the effect of community pharmacists' contributions to reviewing medications and improving the health of older adults.Peer reviewe

Host phenotype characteristics and MC1R in relation to early-onset basal cell carcinoma.

Basal cell carcinoma (BCC) incidence is increasing, particularly among adults under the age of 40 years. Pigment-related characteristics are associated with BCC in older populations, but epidemiologic studies among younger individuals and analyses of phenotype-genotype interactions are limited. We examined self-reported phenotypes and melanocortin 1 receptor gene (MC1R) variants in relation to early-onset BCC. BCC cases (n=377) and controls with benign skin conditions (n=390) under the age of 40 years were identified through Yale's Dermatopathology database. Factors most strongly associated with early-onset BCC were skin reaction to first summer sun for 1 hour (severe sunburn vs. tan odds ratio (OR)=12.27, 95% confidence interval (CI)=4.08-36.94) and skin color (very fair vs. olive OR=11.06, 95% CI=5.90-20.74). Individuals with two or more MC1R non-synonymous variants were 3.59 times (95% CI=2.37-5.43) more likely to have BCC than those without non-synonymous variants. All host characteristics and MC1R were more strongly associated with multiple BCC case status (37% of cases) than a single BCC case status. MC1R, number of moles, skin reaction to first summer sun for 1 hour, and hair and skin color were independently associated with BCC. BCC risk conferred by MC1R tended to be stronger among those with darker pigment phenotypes, traditionally considered to be at low risk of skin cancer

E-health: Determinants, opportunities, challenges and the way forward for countries in the WHO African Region

BACKGROUND: The implementation of the 58(th )World Health Assembly resolution on e-health will pose a major challenge for the Member States of the World Health Organization (WHO) African Region due to lack of information and communications technology (ICT) and mass Internet connectivity, compounded by a paucity of ICT-related knowledge and skills. The key objectives of this article are to: (i) explore the key determinants of personal computers (PCs), telephone mainline and cellular and Internet penetration/connectivity in the African Region; and (ii) to propose actions needed to create an enabling environment for e-health services growth and utilization in the Region. METHODS: The effects of school enrolment, per capita income and governance variables on the number of PCs, telephone mainlines, cellular phone subscribers and Internet users were estimated using a double-log regression model and cross-sectional data on various Member States in the African Region. The analysis was based on 45 of the 46 countries that comprise the Region. The data were obtained from the United Nations Development Programme (UNDP), the World Bank and the International Telecommunications Union (ITU) sources. RESULTS: There were a number of main findings: (i) the adult literacy and total number of Internet users had a statistically significant (at 5% level in a t-distribution test) positive effect on the number of PCs in a country; (ii) the combined school enrolment rate and per capita income had a statistically significant direct effect on the number of telephone mainlines and cellular telephone subscribers; (iii) the regulatory quality had statistically significant negative effect on the number of telephone mainlines; (iv) similarly, the combined school enrolment ratio and the number of telephone mainlines had a statistically significant positive relationship with Internet usage; and (v) there were major inequalities in ICT connectivity between upper-middle, lower-middle and low income countries in the Region. By focusing on the adoption of specific technologies we attempted to interpret correlates in terms of relationships instead of absolute "causals". CONCLUSION: In order to improve access to health care, especially for the majority of Africans living in remote rural areas, there is need to boost the availability and utilization of e-health services. Thus, universal access to e-health ought to be a vision for all countries in the African Region. Each country ought to develop a road map in a strategic e-health plan that will, over time, enable its citizens to realize that vision

Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breast cancer families. We studied the association between breast cancer risk and a PRS based on 75 common genetic variants in 52 Finnish breast cancer families including 427 genotyped women and pedigree information on similar to 4000 additional individuals by comparing the affected to healthy family members, as well as in a case-control dataset comprising 1272 healthy population controls and 1681 breast cancer cases with information on family history. Family structure was summarized using the BOADICEA risk prediction model. The PRS was associated with increased disease risk in women with family history of breast cancer as well as in women within the breast cancer families. The odds ratio (OR) for breast cancer within the family dataset was 1.55 [95 % CI 1.26-1.91] per unit increase in the PRS, similar to OR in unselected breast cancer cases of the case-control dataset (1.49 [1.38-1.62]). High PRS-values were informative for risk prediction in breast cancer families, whereas for the low PRS-categories the results were inconclusive. The PRS is informative in women with family history of breast cancer and should be incorporated within pedigree-based clinical risk assessment.Peer reviewe

Effect of standing posture during whole body vibration training on muscle morphology and function in older adults: A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Whole body vibration (WBV) is a novel modality of exercise shown to improve musculoskeletal function. This study aims to examine the effects of standing posture during low magnitude WBV training on muscle function and muscle morphology in older adults.</p> <p>Methods</p> <p>Nineteen men and women (50-80 years) were recruited to a three month randomised controlled trial and allocated to one of three groups: WBV with flexed knees (FK), WBV with locked knees (LK), or sham WBV with flexed knees (CON). Exposure was intermittent (1 min WBV:1 min rest) for 20 min, three times per week for 13 weeks. Measurements were taken at baseline and at three months. Primary outcomes included upper and lower body muscle function (strength, power and velocity). Secondary outcomes were muscle morphology, balance, habitual and maximal gait velocity, stair climb power, and chair stand performance.</p> <p>Results</p> <p>Sixteen subjects completed the study. Relative (%) upper body contraction velocity improved significantly after WBV with FK compared to LK (FK 16.0%, LK -7.6%, CON 4.7, p = 0.01). Relative upper body strength (LK 15.1%, p = 0.02; FK 12.1%, p = 0.04; CON 4.7%) increased significantly following WBV compared to control. Absolute (p = 0.05) and relative (p = 0.03) lower leg strength significantly improved with both standing postures (LK 14.4%; FK 10.7%; CON 1.3%). Only the LK group differed significantly from CON in relative leg strength gains (p = 0.02). Potentially clinically meaningful but statistically non-significant improvements in lower leg muscle cross-sectional area (LK 3.7 cm², FK 2.4 cm², CON 2.2 cm²p = 0.13) were observed after WBV with LK compared to the other groups. No significant effects of WBV on any functional performance tests were observed.</p> <p>Conclusions</p> <p>Our results suggest that WBV may improve muscle strength and contraction velocity in some muscle groups in older adults. However, hypothesised differential adaptation to standing posture (FK > LK) was observed only for upper body contraction velocity, making recommendations regarding this prescriptive element inconclusive. The efficacy, mechanism of action and long term feasibility of WBV for musculoskeletal health in older adults warrants continued investigation in robustly designed, sufficiently powered future studies.</p> <p>Trial Registration</p> <p>ACTRN12609000353291.</p

RAD51B in Familial Breast Cancer.

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

© 2019, The Author(s). Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors