Objective:To summarize the best available evidence regarding the effectiveness of interventions for preventing frailty progression in older adults.Introduction:Frailty is an age-related state of decreased physiological reserves characterized by an increased risk of poor clinical outcomes. Evidence supporting the malleability of frailty, its prevention and treatment, has been presented.Inclusion criteria:The review considered studies on older adults aged 65 and over, explicitly identified as pre-frail or frail, who had been undergoing interventions focusing on the prevention of frailty progression. Participants selected on the basis of specific illness or with a terminal diagnosis were excluded. The comparator was usual care, alternative therapeutic interventions or no intervention. The primary outcome was frailty. Secondary outcomes included: (i) cognition, quality of life, activities of daily living, caregiver burden, functional capacity, depression and other mental health-related outcomes, self-perceived health and social engagement; (ii) drugs and prescriptions, analytical parameters, adverse outcomes and comorbidities; (iii) costs, and/or costs relative to benefits and/or savings associated with implementing the interventions for frailty. Experimental study designs, cost effectiveness, cost benefit, cost minimization and cost utility studies were considered for inclusion.Methods:Databases for published and unpublished studies, available in English, Portuguese, Spanish, Italian and Dutch, from January 2001 to November 2015, were searched. Critical appraisal was conducted using standardized instruments from the Joanna Briggs Institute. Data was extracted using the standardized tools designed for quantitative and economic studies. Data was presented in a narrative form due to the heterogeneity of included studies.Results:Twenty-one studies, all randomized controlled trials, with a total of 5275 older adults and describing 33 interventions, met the criteria for inclusion. Economic analyses were conducted in two studies. Physical exercise programs were shown to be generally effective for reducing or postponing frailty but only when conducted in groups. Favorable effects on frailty indicators were also observed after the interventions, based on physical exercise with supplementation, supplementation alone, cognitive training and combined treatment. Group meetings and home visits were not found to be universally effective. Lack of efficacy was evidenced for physical exercise performed individually or delivered one-to-one, hormone supplementation and problem solving therapy. Individually tailored management programs for clinical conditions had inconsistent effects on frailty prevalence. Economic studies demonstrated that this type of intervention, as compared to usual care, provided better value for money, particularly for very frail community-dwelling participants, and had favorable effects in some of the frailty-related outcomes in inpatient and outpatient management, without increasing costs.Conclusions:Th...

The possible relationship between diabetes mellitus and cancer risk has long been discussed (Kessler, 1970(Kessler, , 1971 Armstrong et al., 1976;Ragozzino et al., 1982;Green & Hougaard, 1984;O'Mara et al., 1985;Levine et al., 1990;Moss et al., 1991; Davey Smith et al., 1992), but there is still a need for quantitative and precise assessment of the risk. This is not surprising, since several studies were based only on anecdotal reports, and most prospective studies of diabetics are based on at most a few hundred cases of all cancers combined (Armstrong et al., 1976;Ragozzino et al., 1982;Green & Hougaard, 1984;Levine et al., 1990;Moss et al., 1991), thus making any precise inference about specific cancer sites difficult.The largest data set, and hence the most informative study from the viewpoint of statistical power, was based on 8,220 male and 6,690 female cancer cases and about 5,000 controls admitted to the Roswell Park Memorial Institute between 1957 and 1965(O'Mara et al., 1985. In that study, there was a significant risk of endometrial cancer among subjects with a history of diabetes (relative risk, RR 2.0). Significntly elevated nsks of kidney and non-melanomatous skin cancers also emerged in females, but not in males. There was no significnt excess of pancreatic cancer, which however was associated with diabetes mellitus in a few other studies (Kessler, 1970;Wynder et al., 1973;Whittemore et al., 1983;Cuzick & Babiker, 1989 An association between diabetes and primary liver cancer has also been reported in some studies (Lawson et al., 1986; La Vecchia et al., 1990a;Yu et al., 1991) To provide further quantitative information on the issue, and give a further summary overview of the impact of diabetes on the risk of cancers of several sites, we consider in this article data from a case-control study conducted in Northern Italy. S andThe data were derived from an ongoing integrated series of case-control studies, based on a network of teaching and general hospitals in the Greater Milan area. Recruitment of cases with cancer of various sites and of the corresponding controls started between 1983 and 1985, and the present report includes data collected until December, 1992.The general design of this investigation has already been described , and papers on selected cancer sites have already included some information on diabetes (Paramni et al., 1989; Franceschi et al., 1990; La Vecchia et al., 1990a. Briefly, trained interviewers identified and questioned cases with cancer of a number of selected sites and controls admitted to hospital for a wide spectrum of acute, non-neoplastic, non-metabolic, non-hormone-related conditions. On average, less than 4% of eligible subjects (cases and controls) refused to be interviewed. Over 85% of both cases and controls resided in the same region, Lombardy. The same scheme, criteria for identification and recruitment of cases and controls and interview setting (in hospital) was utilised for all the studies considered. All questionnaires included the same structured secti...

The relationship between cancer risk and frequency of consumption of green vegetables and fruit has been analyzed using data from an integrated series of case-control studies conducted in northern Italy between 1983 and 1990. The overall dataset included the following histologically confirmed cancers: oral cavity and pharynx, 119; oesophagus, 294; stomach, 564; colon, 673; rectum, 406; liver, 258; gall-bladder, 41; pancreas, 303; larynx, 149; breast, 2,860; endometrium, 567; ovary, 742; prostate, 107; bladder, 365; kidney, 147; thyroid, 120; Hodgkin's disease, 72; non-Hodgkin lymphomas, 173; myelomas, 117; and a total of 6,147 controls admitted to hospital for acute non-neoplastic conditions, unrelated to long-term dietary modifications. Multivariate relative risks (RR) for subsequent tertiles of vegetable and fruit consumption were derived after allowance for age, sex, area of residence, education and smoking. For vegetables, there was a consistent pattern of protection for all epithelial cancers, with RRs in the upper tertile ranging from 0.2 for oesophagus, liver and larynx to 0.7 for breast. All the trends in risk were in the same direction and significant for all carcinomas except gall-bladder. In contrast, no protection was afforded by high vegetable consumption against non-epithelial lymphoid neoplasms. With reference to fruit, strong inverse relationships were observed for cancers of the upper digestive and respiratory tract, with RRs in the upper tertile between 0.2 and 0.3 for oral cavity and pharynx, oesophagus and larynx relative to the lowest tertile. The lower the location of the tumour in the digestive tract, the weaker appeared to be the protection afforded. Significant inverse relationships were observed for liver, pancreas, prostate and urinary sites, but not for rectum, breast and female genital cancers or thyroid. No relationship emerged for lymphomas and myelomas. Even in the absence of a clear biological interpretation, the consistency and strength of the patterns observed indicate that, in this population, frequent green vegetable intake is associated with a substantial reduction of risk for several common epithelial cancers, and that fruit intake has a favourable effect, especially on upper digestive cancers and, probably, also on urinary tract neoplasms.

Dietary factors in the aetiology of stomach cancer were investigated using data from a case-control study conducted in Northern Italy on 206 histologically confirmed carcinomas and 474 control subjects in hospital for acute, non-digestive conditions, unrelated to any of the potential risk factors for gastric cancer. Dietary histories concerned the frequency of consumption per week of 29 selected food items (including the major sources of starches, proteins, fats, fibres, vitamins A and C, nitrates and nitrites in the Italian diet) and subjective scores for condiments and salt intake. Pasta and rice (the major sources of starch), polenta (a porridge made of maize) and ham were positively related with gastric cancer risk, whereas green vegetables and fresh fruit as a whole (and specifically citrus fruit) and selected fibre-rich aliments (such as whole-grain bread or pasta) showed protective effects on gastric cancer risk. Allowance for major identified potential distorting factors (chiefly indicators of socio-economic status) reduced the positive association with pasta or rice consumption, but did not appreciably modify any of the other risk estimates. When a single logistic model was fitted including all food items significant in univariate analysis, the 3 items remaining statistically significant were green vegetables (relative risk, RR = 0.27 for upper vs. lower tertile), polenta (RR = 2.32) and ham (RR = 1.60). Indices of beta-carotene and ascorbate intake were negatively and strongly related with gastric cancer risk, but the association with these micronutrients was no longer evident after simultaneous allowance for various food items. An approximately 7-fold difference in risk was found between extreme quintiles of a scale measuring major positive and negative associations.

In view of the persisting uncertainty concerning possible mechanisms by which high vegetable and fruit intake decreases cancer risk, foods with divergent values for potentially important micronutrients are a priority for investigation. Tomatoes are low in beta-carotene, but high in lycopene, an active antioxidative agent. In order to assess the effect of tomatoes on risk of cancers of the digestive tract, data were analyzed from an integrated series of case-control studies conducted between 1985 and 1991 in northern Italy, where tomato intake is high but, also, heterogeneous. The overall dataset included the following histologically confirmed cancer cases: oral cavity and pharynx, 314; esophagus, 85; stomach, 723; colon, 955; and rectum, 629; and a total of 2,879 controls admitted to hospital for acute non-neoplastic or non-digestive conditions, unrelated to long-term dietary modifications. Multivariate odds ratios (OR) and 95% confidence interval (CI) for subsequent quartiles of intake of raw tomatoes were derived, after allowance for age, sex, study center, education, smoking and drinking level, and tertile of total caloric intake. There was a consistent pattern of protection for all sites (OR in the upper quartile ranging between 0.4 and 0.7), most notably for gastrointestinal neoplasms. All trends in risk were highly significant. The beneficial effect of raw tomatoes in this population may be partly due to the fact that they constitute perhaps the most specific feature of the Mediterranean diet. However, if it is true that tomatoes protect against digestive-tract cancers, this is of interest from both a scientific and a public health viewpoint.

Little is known about the use of antidepressant drugs in Italy since the introduction of selective serotonin reuptake inhibitors (SSRIs). To fill this gap, we examined antidepressant drug sales data from 1988 to 1996 for the whole country, and for the years 1995 and 1996 on the regional level. National suicide trends from 1988 to 1994 were also examined to assess whether the increasing use of SSRI antidepressants was associated with changes in suicide rates. From 1988 to 1996 an increase of antidepressant sales of 53% was recorded. This increase reflected increasing use of SSRIs, which in 1996 accounted for more than 30% of total antidepressants sold. The analysis of regional differences demonstrated heterogeneity between north, center, and south. In the south prescriptions of antidepressants and use of SSRIs were lower than in the rest of the country. In the 7-year period over which SSRI use increased, male suicide rates increased from 9.8 to 10.2 per 100,000 inhabitants, and female suicide rates declined from 3.9 to 3.2 per 100,000. These data suggest that SSRIs gave a new impetus to antidepressant sales. However, possible public health benefits related to the shift from old to new antidepressants have yet to be demonstrated.

SummaryThe relationship between estimated intake of selected micronutrients and the risk of colorectal cancer was analysed using data from a case-control study conducted in northern Italy. The There are indications that several micronutrients may influence the process of colorectal carcinogenesis. These include a potential protective effect of folate (Benito et al., 1991;Freudenheim et al., 1991), a co-factor in the methylation of thymidylate for DNA synthesis and the production of S-adenosylmethionine, the primary methyl donor in the body (Cooper, 1983); of calcium, which may react with fatty acids to form insoluble soaps (Newmark et al., 1984;Garland et al., 1985;Sorenson et al., 1988); and of ascorbic acid, Pcarotene and vitamin E, which may act as antioxidants (Iscovich et al., 1992;Longnecker et al., 1992). Two companion cohort studies (Giovannucci et al., 1993), including 564 women and 331 men with colorectal adenoma, have also suggested that folate may have a specific favourable effect on preneoplastic large bowel lesions. No convincing association for any micronutrients, however, has emerged from other studies (Peters et al., 1992), and the issue is therefore still unsettled, particularly since most studies did not make adequate allowance for various micronutrients.To provide further data on the issue, we have considered the role of selected micronutrients on colorectal carcinogenesis using data from a case-control study conducted in the greater Milan area, previously considered with reference to intake of specific foods (La Vecchia et al., 1988 The control group included patients admitted for a wide spectrum of acute, non-neoplastic, non-digestive tract conditions to the same network of hospitals where cases had been identified. Of these, 47% were admitted for traumatic conditions, 20% had non-traumatic orthopaedic diseases, 19% had acute surgical conditions, and 14% had other miscellaneous disorders. A total of 2,024 controls were included in the present analysis. The age range was 19-74 years, and the median age was 55 years. The catchment areas of cases and controls were comparable: over 80% of cases and controls resided in Lombardy, and over 90% came from northern Italy. Less than 3% of eligible subjects (cases and controls) refused to be interviewed.Trained interviewers used a structured questionnaire to obtain information on general sociodemographic factors and lifestyle habits, weight and height, a problem-oriented medical history and family history of colorectal cancer. Further, information on the frequency of consumption per week of 29 indicator foods was collected. These included major sources of P-carotene, retinol, ascorbic acid, vitamins D and E, folate, methionine and calcium in the Italian diet. We computed nutrient intake by multiplying the consumption frequency of each unit of food by the nutrient content of the standard average portions, using composition values from the Italian composition tables (Fidanza & Verdiglioni, 1988), with the integration of other sources when these were no...

This study indicates that a family history of MI is an independent risk factor for MI, and that the number of relatives and the age at which they were affected is related to the strength of the association. There is a multiplicative effect on RR between family history and several major risk factors for MI.