The Association Between Polypharmacy and Physical Function in Older Adults: a Systematic Review.

BACKGROUND: Reduced physical function and polypharmacy (PPha) are two highly prevalent negative effects of aging, which are expected to increase more, since demographic aging is expected to grow rapidly within the next decades. Previous research suggests that polypharmacy (PPha) is a predictor of poor physical function and vice versa in older adults and therefore we conducted a systematic review of the literature to summarize and critically analyze the relationship between physical function and PPha and vice versa in older adults, in order to provide recent scientific evidence. METHODS: We searched MEDLINE and Embase from their inception to 19th October 2018 for English-language observational studies or trials assessing the effect of PPha on physical function and vice versa in older adults. Two investigators independently extracted study data and assessed the quality of the studies, after having screened the available studies from the literature search. Any disagreement was resolved by consensus. RESULTS: Eighteen observational studies met the inclusion criteria. Eight studies assessed the impact of physical function on PPha and ten studies assessed the impact of PPha on physical function. Regarding the studies with PPha measurements as the outcome, all of them, except for one, found that better physical function is associated with lower risk of PPha. Likewise, all the studies with physical function measurements as the outcome, except for one, suggested that PPha is associated with lower physical function. DISCUSSION: Evidence examining the effect of PPha on physical function and vice versa in older adults suggests a strong bidirectional association between these two factors and clinicians should be aware of this strong relationship. The limitations of our study include the high variability in PPha definitions and physical function measures, and the treatment of PPha and physical function as constant instead of time-varying variables in the studies' analyses.

Association between muscular strength and depressive symptoms : A narrative review.

There is increasing evidence for an association between low muscular strength and depressive symptoms. In this review the existing literature on the association between muscular strength and depression particularly in older people as reported in epidemiological studies is summarized. From the literature search, conducted in PubMed (January 1980-May 2018), 17 papers (8 cross-sectional and 9 longitudinal studies) were selected. All cross-sectional studies reported significantly lower odds of having depressive symptoms with increased levels of muscular strength and this association persisted even after adjusting for several confounders including the level of physical activity. The majority of the longitudinal studies also reported that low muscular strength was independently associated with a higher risk of developing depression but more studies are needed to confirm this evidence. Furthermore, future investigations are needed to explore the exact mechanisms of muscular strength in relation to depression. Low muscular strength is a modifiable factor for depression, which is of great public health interest.

Physical activity and lung cancer among non-smokers: a pilot molecular epidemiological study within EPIC.

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by (32)P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.90), higher GSH levels (+1.87 micromol GSH g(-1) haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38-2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84-1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.

Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study.

In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0.02), vitamin E (P = 0.04) and alcohol (P = 0.03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0.03, 0.04, and 0.03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.

Dietary patterns and survival of older Europeans: the EPIC-Elderly Study (European Prospective Investigation into Cancer and Nutrition).

OBJECTIVE: To investigate the association of a posteriori dietary patterns with overall survival of older Europeans. DESIGN AND SETTING: This is a multi-centre cohort study. Cox regression analysis was used to investigate the association of the prevailing, a posteriori-derived, plant-based dietary pattern with all-cause mortality in a population of subjects who were 60 years or older at recruitment to the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort). Analyses controlled for all known potential risk factors. SUBJECTS: In total, 74,607 men and women, 60 years or older at enrolment and without previous coronary heart disease, stroke or cancer, with complete information about dietary intakes and potentially confounding variables, and with known survival status as of December 2003, were included in the analysis. RESULTS: An increase in the score which measures the adherence to the plant-based diet was associated with a lower overall mortality, a one standard deviation increment corresponding to a statistically significant reduction of 14% (95% confidence interval 5-23%). In country-specific analyses the apparent association was stronger in Greece, Spain, Denmark and The Netherlands, and absent in the UK and Germany. CONCLUSIONS: Greater adherence to the plant-based diet that was defined a posteriori in this population of European elders is associated with lower all-cause mortality. This dietary score is moderately positively correlated with the Modified Mediterranean Diet Score that has been constructed a priori and was also shown to be beneficial for the survival of the same EPIC-Elderly cohort.

Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study.

BACKGROUND: Several countries are discussing new legislation on the ban of smoking in public places, and on the acceptable levels of traffic-related air pollutants. It is therefore useful to estimate the burden of disease associated with indoor and outdoor air pollution. METHODS: We have estimated exposure to Environmental Tobacco Smoke (ETS) and to air pollution in never smokers and ex-smokers in a large prospective study in 10 European countries (European Prospective Investigation into Cancer and Nutrition)(N = 520,000). We report estimates of the proportion of lung cancers attributable to ETS and air pollution in this population. RESULTS: The proportion of lung cancers in never- and ex-smokers attributable to ETS was estimated as between 16 and 24%, mainly due to the contribution of work-related exposure. We have also estimated that 5-7% of lung cancers in European never smokers and ex-smokers are attributable to high levels of air pollution, as expressed by NO2 or proximity to heavy traffic roads. NO2 is the expression of a mixture of combustion (traffic-related) particles and gases, and is also related to power plants and waste incinerator emissions. DISCUSSION: We have estimated risks of lung cancer attributable to ETS and traffic-related air pollution in a large prospective study in Europe. Information bias can be ruled out due to the prospective design, and we have thoroughly controlled for potential confounders, including restriction to never smokers and long-term ex-smokers. Concerning traffic-related air pollution, the thresholds for indicators of exposure we have used are rather strict, i.e. they correspond to the high levels of exposure that characterize mainly Southern European countries (levels of NO2 in Denmark and Sweden are closer to 10-20 ug/m3, whereas levels in Italy are around 30 or 40, or higher).Therefore, further reduction in exposure levels below 30 ug/m3 would correspond to additional lung cancer cases prevented, and our estimate of 5-7% is likely to be an underestimate. Overall, our prospective study draws attention to the need for strict legislation concerning the quality of air in Europe.

Air pollution and risk of lung cancer in a prospective study in Europe.

To estimate the relationship between air pollution and lung cancer, a nested case-control study was set up within EPIC (European Prospective Investigation on Cancer and Nutrition). Cases had newly diagnosed lung cancer, accrued after a median follow-up of 7 years among the EPIC ex-smokers (since at least 10 years) and never smokers. Three controls per case were matched. Matching criteria were gender, age (+/-5 years), smoking status, country of recruitment and time elapsed between recruitment and diagnosis. We studied residence in proximity of heavy traffic roads as an indicator of exposure to air pollution. In addition, exposure to air pollutants (NO(2), PM10, SO(2)) was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Cotinine was measured in plasma. We found a nonsignificant association between lung cancer and residence nearby heavy traffic roads (odds ratio = 1.46, 95% confidence interval, CI, 0.89-2.40). Exposure data for single pollutants were available for 197 cases and 556 matched controls. For NO(2) we found an odds ratio of 1.14 (95% CI, 0.78-1.67) for each increment of 10 microg/m(3), and an odds ratio of 1.30 (1.02-1.66) for concentrations greater than 30 microg/m(3). The association with NO(2) did not change after adjustment by cotinine and additional potential confounders, including occupational exposures. No clear association was found with other pollutants.

Fruits and vegetables and renal cell carcinoma: findings from the European prospective investigation into cancer and nutrition (EPIC).

We examined the association between fruits and vegetables and risk of renal cell carcinoma (RCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake data and complete follow-up information on cancer incidence were available for 375,851 participants recruited in EPIC centers of 8 countries. During an average follow-up of 6.2 years, 306 incident cases of RCC were identified. The associations of consumption of total vegetables, total fruits, combined total fruits and vegetables and specific subtypes of vegetables with RCC risk were analyzed using Cox proportional hazards, stratified by centre and adjusted for potential confounders. No significant associations between fruit and vegetable consumption and RCC risk were observed despite a wide range of intake. The estimated relative risks (95% confidence intervals [CI]) in men and women combined were 0.97 (0.85-1.11) per 40 g increase in vegetable intake, 1.03 (0.97-1.08) per 40 g increase in fruit intake and 1.02 (0.93-1.11) per 80 g increase in fruit and vegetable intake combined. Among the vegetable subtypes, an inverse association was observed for root vegetables (RR per 8 g increase: 0.88; 95% CI: 0.78-0.99). These results suggest that total consumption of fruits and vegetables is not related to risk of RCC, although we cannot exclude the possibility that very low consumption is related to higher risk. The relationship of specific fruit and vegetable subgroups with RCC risk warrant further investigation.

DNA adducts and lung cancer risk: a prospective study.

Objectives were to investigate prospectively the ability of DNA adducts to predict cancer and to study the determinants of adducts, especially air pollutants. DNA adducts were measured in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) investigation. Cases included newly diagnosed lung cancer (n = 115), upper respiratory cancers (pharynx and larynx; n = 82), bladder cancer (n = 124), leukemia (n = 166), and chronic obstructive pulmonary disease or emphysema deaths (n = 77) accrued after a median follow-up of 7 years among the EPIC former smokers and never-smokers. Three controls per case were matched for questionnaire analyses and two controls per case for laboratory analyses. Matching criteria were gender, age, smoking status, country of recruitment, and follow-up time. Individual exposure to air pollution was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Leukocyte DNA adducts were analyzed blindly using 32P postlabeling technique. Adducts were associated with the subsequent risk of lung cancer, with an odds ratio (OR) of 1.86 [95% confidence interval (95% CI), 0.88-3.93] when comparing detectable versus nondetectable adducts. The association with lung cancer was stronger in never-smokers (OR, 4.04; 95% CI, 1.06-15.42) and among the younger age groups. After exclusion of the cancers occurring in the first 36 months of follow-up, the OR was 4.16 (95% CI, 1.24-13.88). A positive association was found between DNA adducts and ozone (O3) concentration. Our prospective study suggests that leukocyte DNA adducts may predict lung cancer risk of never-smokers. Besides, the association of DNA adduct levels with O3 indicates a possible role for photochemical smog in determining DNA damage.

Fruits and vegetables and lung cancer: Findings from the European Prospective Investigation into Cancer and Nutrition.

Intake of fruits and vegetables is thought to protect against the development of lung cancer. However, some recent cohort and case-control studies have shown no protective effect. We have assessed the relation between fruit and vegetable intake and lung cancer incidence in the large prospective investigation on diet and cancer, the European Prospective Investigation Into Cancer and Nutrition (EPIC). We studied data from 478,021 individuals that took part in the EPIC study, who were recruited from 10 European countries and who completed a dietary questionnaire during 1992-1998. Follow-up was to December 1998 or 1999, but for some centres with active follow-up to June 2002. During follow-up, 1,074 participants were reported to have developed lung cancer, of whom 860 were eligible for our analysis. We used the Cox proportional hazard model to determine the effect of fruit and vegetable intake on the incidence of lung cancer. We paid particular attention to adjustment for smoking. Relative risk estimates were obtained using fruit and vegetable intake categorised by sex-specific, cohort-wide quintiles. After adjustment for age, smoking, height, weight and gender, there was a significant inverse association between fruit consumption and lung cancer risk: the hazard ratio for the highest quintile of consumption relative to the lowest being 0.60 (95% Confidence Interval 0.46-0.78), p for trend 0.0099. The association was strongest in the Northern Europe centres, and among current smokers at baseline, and was strengthened when the 293 lung cancers diagnosed in the first 2 years of follow-up were excluded from the analysis. There was no association between vegetable consumption or vegetable subtypes and lung cancer risk. The findings from this analysis can be regarded as re-enforcing recommendations with regard to enhanced fruit consumption for populations. However, the effect is likely to be small compared to smoking cessation.