Congenital rhabdomyosarcoma: A report from the European paediatric Soft tissue sarcoma Study Group.

PROCEDURE: Congenital rhabdomyosarcoma (RMS) represents a challenging disease due to its characteristics and the difficulties in delivering treatment in this immature population. METHODS: We analyzed treatment and outcome of patients with congenital RMS, defined as tumor diagnosed in the first 2 months of life, enrolled in the European paediatric Soft tissue sarcoma Study Group protocols. RESULTS: Twenty-four patients with congenital RMS were registered. All, except one patient (PAX3-FOXO1-positive metastatic RMS), had favorable histology and localized disease. Three patients had VGLL2-CITED2/NCOA2 fusion. Complete tumor resection was achieved in 10 patients. No radiotherapy was given. Chemotherapy doses were adjusted to age and weight. Only two patients required further dose reduction for toxicity. The 5-year event-free survival (EFS) and overall survival (OS) were 75.0% (95% confidence interval [CI] 52.6-87.9) and 87.3% (95% CI 65.6-95.7), respectively. Progressive disease was the main cause of treatment failure. CONCLUSION: Patients with congenital RMS presented with a favorable disease, allowing weight- and age-adjusted doses of chemotherapy and avoidance of irradiation, without compromising the outcome.

Using the Multidimensional Prognostic Index (MPI) to improve cost-effectiveness of interventions in multimorbid frail older persons: results and final recommendations from the MPI_AGE European Project.

MPI_AGE is a European Union co-funded research project aimed to use the Multidimensional Prognostic Index (MPI), a validated Comprehensive Geriatric Assessment (CGA)-based prognostic tool, to develop predictive rules that guide clinical and management decisions in older people in different European countries. A series of international studies performed in different settings have shown that the MPI is useful to predict mortality and risk of hospitalization in community-dwelling older subjects at population level. Furthermore, studies performed in older people who underwent a CGA before admission to a nursing home or receiving homecare services showed that the MPI successfully identified groups of persons who could benefit, in terms of reduced mortality, of specific therapies such as statins in diabetes mellitus and coronary artery disease, anticoagulants in atrial fibrillation and antidementia drugs in cognitive decline. A prospective trial carried out in nine hospitals in Europe and Australia demonstrated that the MPI was able to predict not only in-hospital and long-term mortality, but also institutionalization, re-hospitalization and receiving homecare services during the one-year follow-up after hospital discharge. The project also explored the association between MPI and mortality in hospitalized older patients in need of complex procedures such as transcatheter aortic valve implantation or enteral tube feeding. Evidence from these studies has prompted the MPI_AGE Investigators to formulate recommendations for healthcare providers, policy makers and the general population which may help to improve the cost-effectiveness of appropriate health care interventions for older patients.

Enteral tube feeding and mortality in hospitalized older patients: A multicenter longitudinal study.

BACKGROUND & AIMS: The literature regarding enteral nutrition and mortality in older frail people is limited and still conflicting. Moreover, the potential role of comprehensive geriatric assessment is poorly explored. We therefore aimed to investigate whether the Multidimensional Prognostic Index (MPI), an established tool that assesses measures of frailty and predicts mortality, may help physicians in identifying patients in whom ETF (enteral tube feeding) is effective in terms of reduced mortality. METHODS: Observational, longitudinal, multicenter study with one year of follow-up. Data regarding ETF were recorded through medical records. A standardized comprehensive geriatric assessment was used to calculate the MPI. Participants were divided in low (MPI-1), moderate (MPI-2) or severe (MPI-3) risk of mortality. Data regarding mortality were recorded through administrative information. RESULTS: 1064 patients were included, with 79 (13 in MPI 1-2 and 66 in MPI-3 class) receiving ETF. In multivariable analysis, patients receiving ETF experienced a higher risk of death (odds ratio, OR = 2.00; 95% confidence intervals, CI: 1.19-3.38). However, after stratifying for their MPI at admission, mortality was higher in MPI-3 class patients (OR = 2.03; 95%CI: 1.09-3.76), but not in MPI 1-2 class patients (OR = 1.51; 95%CI: 0.44-5.25). The use of propensity score confirmed these findings. CONCLUSIONS: ETF is associated with a higher risk of death. However, this is limited to more frail patients, suggesting the importance of the MPI in the prognostic evaluation of ETF.

Older women are frailer, but less often die then men: a prospective study of older hospitalized people.

OBJECTIVES: The association between frailty, mortality and sex is complex, but a limited literature is available on this topic, particularly for older hospitalized patients. Therefore, the objective of our study was to prospectively evaluate sex differences in frailty, assessed by the Multidimensional Prognostic Index (MPI) and mortality, institutionalization, and re-hospitalization in an international cohort of older people admitted to hospital. STUDY DESIGN: We used data from nine public hospitals in Europe and Australia, to evaluate sex differences in mortality, frailty and the risk of institutionalization and re-hospitalization, during one year of follow-up. MAIN OUTCOME MEASURES: People aged 65 years or more admitted to hospital for an acute medical condition or for a relapse of a chronic disease were included. A standardized comprehensive geriatric assessment, which evaluated functional, nutritional, and cognitive status, risk of pressure sores, comorbidities, medications and co-habitation status, was used to calculate the MPI to measure frailty in all hospitalized older people. Data regarding mortality, institutionalization and re-hospitalization were also recorded for one year. RESULTS: Altogether, 1140 hospitalized patients (mean age = 84.2 years; 694 women = 60.9%) were included. The one-year mortality rate was 33.2%. In multivariate analysis, adjusted for age, MPI score, centre and diagnosis at baseline, although women had higher MPI scores than men, the latter had higher in-hospital (odds ratio, OR = 2.26; 95% confidence intervals, CI = 1.27-4.01) and one-year post-discharge mortality (OR = 2.04; 95%CI = 1.50-2.79). Furthermore, men were less frequently institutionalized in a care home than female patients (OR = 0.55; 95%CI: 0.34-0.91), but they were also more frequently re-hospitalized (OR = 1.42; 95%CI: 1.06-1.91) during the year after hospital discharge. CONCLUSION: Older hospitalized men were less frail, but experienced higher in-hospital and one-year mortality than women. Women were admitted more frequently to nursing homes and experienced a lower risk of re-hospitalization. These findings suggest important differences between the sexes and extends the 'male-female health-survival paradox' to acutely ill patient groups.

Using the Multidimensional Prognostic Index to Predict Clinical Outcomes of Hospitalized Older Persons: A Prospective, Multicenter, International Study.

BACKGROUND: Multidimensional Prognostic Index (MPI) is useful as a prognostic tool in hospitalized older patients, but our knowledge is derived from retrospective studies. We therefore aimed to evaluate in a multicenter, longitudinal, cohort study whether the MPI at hospital admission is useful to identify groups with different mortality risk and whether MPI at discharge may predict institutionalization, rehospitalization, and use of home care services during 12 months. METHODS: This longitudinal study, carried out between February 2015 and August 2017, included nine public hospitals in Europe and Australia. A standardized comprehensive geriatric assessment including information on functional, nutritional, cognitive status, risk of pressure sores, comorbidities, medications, and cohabitation status was used to calculate the MPI and to categorize participants in low, moderate, and severe risk of mortality. Data regarding mortality, institutionalization, rehospitalization, and use of home care services were recorded through administrative information. RESULTS: Altogether, 1,140 hospitalized patients (mean age 84.1 years, women = 60.8%) were included. In the multivariable analysis, compared to patients with low risk group at admission, patients in moderate (odds ratio [OR] = 3.32; 95% CI: 1.79-6.17; p < .001) and severe risk (OR = 10.72, 95% CI: 5.70-20.18, p < .0001) groups were at higher risk of overall mortality. Among the 984 older patients with follow-up data available, those in the severe-risk group experienced a higher risk of overall mortality, institutionalization, rehospitalization, and access to home care services. CONCLUSIONS: In this cohort of hospitalized older adults, higher MPI values are associated with higher mortality and other negative outcomes. Multidimensional assessment of older people admitted to hospital may facilitate appropriate clinical and postdischarge management.

Effects of oral amino acid supplementation on Multidimensional Prognostic Index in hospitalized older patients: a multicenter randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: It is not known whether amino acid supplementations may influence health status in hospitalized older acutely ill patients. AIM: The aim of this study was to determine whether nutritional supplementation with amino acids (Aminoglutam®) is associated with multidimensional improvement assessed with the Multidimensional Prognostic Index (MPI). METHODS: In this randomized, double-blind, placebo-controlled pilot clinical trial, 126 patients aged ≥65 years were enrolled from 6 Italian geriatric wards. A multidimensional assessment to calculate the MPI was performed at baseline and after 4 weeks of treatment with nutritional supplementation (96 kcal, 12 g amino acids, 0.18 g fat, 11.6 g carbohydrate, and vitamins B1, B6, and C) or placebo administered twice a day. Logistic regression modeling was applied to determine the effect of treatment on the improvement of MPI (vs no-change/worsening), adjusting for gender, age, and MPI at baseline. Treatment's interactions with age, gender, and MPI at baseline were tested adding the appropriate interaction parameter in the regression models. RESULTS: Of the 126 patients included, 117 patients (93%) completed the study. A significant improvement in the MPI score was detected in the overall population (mean difference post-pretreatment: -0.03, p=0.001), with no differences between active and placebo arms. Men in the amino acid supplementation group had a significantly higher rate of improvement in MPI (81%) compared to the placebo group (46%) (Fisher's exact test p=0.03). Adjusting for age, diagnosis, and MPI at baseline, amino acid treatment was shown to be associated with an improvement in MPI in men (OR=4.82, 95% confidence interval [CI]: 0.87-26.7) and not in women (OR=0.70, 95% CI: 0.27-1.81). The interaction effect between active treatment and gender was significant (p=0.04). CONCLUSION: A 4-week amino acid supplementation improved the MPI significantly in hospitalized older male patients but not in female patients. Further studies are needed to confirm the gender effect of amino acid supplementation on MPI in older patients.

Multidimensional Prognostic Index and pro-adrenomedullin plasma levels as mortality risk predictors in older patients hospitalized with community-acquired pneumonia: a prospective study.

BACKGROUND: To evaluate the prognostic accuracy of proadrenomedullin (proADM) in comparison with and in addition to the Multidimensional Prognostic Index (MPI), a validated predictive tool for mortality derived from a comprehensive geriatric assessment (CGA) to predict one-month mortality risk in older patients hospitalized with community-acquired pneumonia (CAP). METHODS: All patients aged 65 years and older, consecutively admitted to an acute geriatric ward with a diagnosis of CAP from February to July 2012. At admission and at discharge they were submitted to a standard CGA in order to calculate MPI. Moreover, plasma samples were taken at baseline and after one, three and five days of hospitalization for the analysis of pro-ADM. RESULTS: Fifty patients (mean age 86.2±7.5 years), with 31 at high risk of mortality (MPI-3) were enrolled. ProADM and MPI, both at admission and at discharge, were significant predictor of mortality. As expected, MPI at admission showed lower predictive accuracy than MPI at discharge (survival C-statistic 0.667 vs. 0.851). The addition of proADM to the MPI at admission significantly increased accuracy in predicting one-month mortality (C-statistics from 0.667 to 0.731, P=0.018 at baseline; from 0.667 to 0.733, P=0.008 at 1 day; from 0.633 to 0.724; P=0.019 at 3 days; from 0.667 to 0.828; P=0.003 at 5 days). Conversely, adding pro-ADM to the MPI at discharge did not significantly improve the model's prognostic accuracy. CONCLUSIONS: ProADM may significantly improve the prognostic accuracy of the MPI at admission in hospitalized elderly patients with CAP.

Combined use of the multidimensional prognostic index (MPI) and procalcitonin serum levels in predicting 1-month mortality risk in older patients hospitalized with community-acquired pneumonia (CAP): a prospective study.

BACKGROUND: Several scores and biomarkers, i.e., procalcitonin (PCT), were proposed to stratify the mortality risk in community-acquired pneumonia (CAP). AIM: Evaluating prognostic accuracy of PCT and Multidimensional Prognostic Index (MPI) for 1-month mortality risk in older patients with CAP. METHODS: At hospital admission and at discharge, patients were evaluated by a Comprehensive Geriatric Assessment to calculate MPI. Serum PCT was measured at admission and 1, 3, and 5 days after hospital admission. RESULTS: 49 patients were enrolled. The overall 1-month mortality was 44.5 for 100-persons year. Mortality rates were higher with the increasing of MPI. In survived patients, MPI at discharge showed higher predictive accuracy than MPI at admission. Adding PCT levels to admission MPI prognostic accuracy for 1-month mortality significantly increased. CONCLUSION: In older patients with CAP, MPI significantly predicted 1 month mortality. PCT levels significantly improved the accuracy of MPI at admission in predicting 1-month mortality.

Association of Antidementia Drugs and Mortality in Community-Dwelling Frail Older Patients With Dementia: The Role of Mortality Risk Assessment.

OBJECTIVE: To evaluate whether treatment with antidementia drugs is associated with reduced mortality in older patients with different mortality risk at baseline. DESIGN: Retrospective. SETTING: Community-dwelling. PARTICIPANTS: A total of 6818 older people who underwent a Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA) evaluation to determine accessibility to homecare services or nursing home admission from 2005 to 2013 in the Padova Health District, Italy were included. MEASUREMENTS: Mortality risk at baseline was calculated by the Multidimensional Prognostic Index (MPI), based on information collected with the SVaMA. Participants were categorized to have mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) mortality risk. Propensity score-adjusted hazard ratios (HR) of 2-year mortality were calculated according to antidementia drug treatment. RESULTS: Patients treated with antidementia drugs had a significant lower risk of death than untreated patients (HR 0.82; 95% confidence interval [CI] 0.73-0.92 and 0.56; 95% CI 0.49-0.65 for patients treated less than 2 years and more than 2 years treatment, respectively). After dividing patients according to their MPI-SVaMA grade, antidementia treatment was significantly associated with reduced mortality in the MPI-SVaMA-1 mild (HR 0.71; 95% CI 0.54-0.92) and MPI-SVaMA-2 moderate risk (HR 0.61; 95% CI 0.40-0.91, matched sample), but not in the MPI-SVaMA-3 high risk of death. CONCLUSIONS: This large community-dwelling patient study suggests that antidementia drugs might contribute to increased survival in older adults with dementia with lower mortality risk.

Three Decades of Comprehensive Geriatric Assessment: Evidence Coming From Different Healthcare Settings and Specific Clinical Conditions.

Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.

The EpSSG NRSTS 2005 treatment protocol for desmoid-type fibromatosis in children: an international prospective case series.

BACKGROUND: In 2005, the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) proposed a conservative treatment algorithm-consisting of an initial wait-and-see strategy, non-mutilating surgery, and minimal-morbidity chemotherapy (in the case of tumour progression)-for paediatric patients with desmoid-type fibromatosis. We aimed to investigate the outcomes of this algorithm. METHODS: In this case series, patients (<25 years) with desmoid-type fibromatosis from 57 centres in eight countries were prospectively registered through a web-based system. Diagnosis was based on histological analysis of the tumour specimen after biopsy or surgery, and we classified patients by tumour site, clinical stage (TNM system), and post-surgical stage (Intergroup Rhabdomyosarcoma Study system). Progression-free survival was defined as the time from diagnosis until disease progression (clinical or radiological progressive disease, relapse, or death from any cause). FINDINGS: From Oct 1, 2005, to July 31, 2016, 173 patients (median age 11·4 years [IQR 4·0-14·1], 88 [51%] male patients) were registered. After excluding patients with missing data, 54 (35%) patients had no immediate therapy (wait-and-see strategy), 47 (31%) had immediate surgery, and 53 (34%) had immediate chemotherapy after diagnosis. 5-year progression-free survival was 36·5% (95% CI 27·8-45·2) overall, 26·7% (14·2-41·0) in the wait-and-see group, 41·2% (25·8-55·9) in the surgery group, and 42·8% (27·2-57·6) in the chemotherapy group (overall log-rank p=0·17; wait-and-see vs surgery p=0·12; wait-and-see vs chemotherapy p=0·13). In multivariable analysis, large tumour size (>5 cm) was associated with worse progression-free survival (hazard ratio 2·25, 95% CI 1·34-3·76; p=0·0021). Apart from one patient in the chemotherapy group who died from a secondary tumour (head and neck anaplastic embryonal rhabdomyosarcoma), all patients were alive at the time of analysis. 13 (8%) patients had biopsy only (no further treatment), 65 (42%) had chemotherapy only, 31 (20%) had surgery only, 36 (23%) had both chemotherapy and surgery, and nine (6%) had radiotherapy in addition to other therapies. INTERPRETATION: In paediatric patients with desmoid-type fibromatosis, the EpSSG conservative strategy did not compromise outcomes and could be adopted to reduce treatment burden. FUNDING: S Wisnia and la Città della Speranza Foundation.

Relation of Statin Use and Mortality in Community-Dwelling Frail Older Patients With Coronary Artery Disease.

Clinical decision-making for statin treatment in older patients with coronary artery disease (CAD) is under debate, particularly in community-dwelling frail patients at high risk of death. In this retrospective observational study on 2,597 community-dwelling patients aged ≥65 years with a previous hospitalization for CAD, we estimated mortality risk assessed with the Multidimensional Prognostic Index (MPI), based on the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA), used to determine accessibility to homecare services/nursing home admission in 2005 to 2013 in the Padua Health District, Veneto, Italy. Participants were categorized as having mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) baseline mortality risk, and propensity score-adjusted hazard ratios (HRs) of 3-year mortality rate were calculated according to statin treatment in these subgroups. Greater MPI-SVaMA scores were associated with lower rates of statin treatment and higher 3-year mortality rate (MPI-SVaMA-1 = 23.4%; MPI-SVaMA-2 = 39.1%; MPI-SVaMA-3 = 76.2%). After adjusting for propensity score quintiles, statin treatment was associated with lower 3-year mortality risk irrespective of MPI-SVaMA group (HRs [95% confidence intervals] 0.45 [0.37 to 0.55], 0.44 [0.36 to 0.53], and 0.28 [0.21 to 0.39] in MPI-SVaMA-1, -2, and -3 groups, respectively [interaction test p = 0.202]). Subgroup analyses showed that statin treatment was also beneficial irrespective of age (HRs [95% confidence intervals] 0.38 [0.27 to 0.53], 0.45 [0.38 to 0.54], and 0.44 [0.37 to 0.54] in 65 to 74, 75 to 84, and ≥85 year age groups, respectively [interaction test p = 0.597]). In conclusion, in community-dwelling frail older patients with CAD, statin treatment was significantly associated with reduced 3-year mortality rate irrespective of age and multidimensional impairment, although the frailest patients were less likely to be treated with statins.

Gastrointestinal Microbiota and Their Contribution to Healthy Aging.

Studies on populations at different ages have shown that after birth, the gastrointestinal (GI) microbiota composition keeps evolving, and this seems to occur especially in old age. Significant changes in GI microbiota composition in older subjects have been reported in relation to diet, drug use and the settings where the older subjects are living, that is, in community nursing homes or in a hospital. Moreover, changes in microbiota composition in the old age have been related to immunosenescence and inflammatory processes that are pathophysiological mechanisms involved in the pathways of frailty. Frailty is an age-related condition of increased vulnerability to stresses due to the impairment in multiple inter-related physiologic systems that are associated with an increased risk of adverse outcomes, such as falls, delirium, institutionalization, hospitalization and death. Preliminary data suggest that changes in microbiota composition may contribute to the variations in the biological, clinical, functional and psycho-social domains that occur in the frail older subjects. Multidimensional evaluation tools based on a Comprehensive Geriatric Assessment (CGA) have demonstrated to be useful in identifying and measuring the severity of frailty in older subjects. Thus, a CGA approach should be used more widely in clinical practice to evaluate the multidimensional effects potentially related to GI microbiota composition of the older subjects. Probiotics have been shown to be effective in restoring the microbiota changes of older subjects, promoting different aspects of health in elderly people as improving immune function and reducing inflammation. Whether modulation of GI microbiota composition, with multi-targeted interventions, could have an effect on the prevention of frailty remains to be further investigated in the perspective of improving the health status of frail 'high risk' older individuals.

Change in the Multidimensional Prognostic Index Score During Hospitalization in Older Patients.

We investigated and describe change in the Multidimensional Prognostic Index (MPI) score between admission and discharge in 960 older patients admitted to 20 geriatric units for an acute disease or a relapse of a chronic disease. The MPI was calculated at admission and at discharge. Subjects were divided into three groups of MPI score, low risk (MPI-1 value ≤0.33), moderate risk (MPI-2 value 0.34-0.66), and severe risk of mortality (MPI-3 value ≥0.67), on the basis of previously established cutoffs. Variation of MPI values over length of hospital stay (LOS) was analyzed with a multivariable longitudinal linear model for repeated measurements. At admission, 23.5% subjects had an MPI-1 score, 33.3% had an MPI-2 score, and 43.0% had an MPI-3 score. Overall, for almost 60% of the patients, MPI score at hospital discharge was different compared with the score at admission, although the difference was not statistically significant (-0.003; p = 0.708). Patients with high and intermediate MPI scores at admission had a decrease of MPI score at discharge (delta-MPI -0.026, p < 0.001, and delta-MPI -0.066, p = 0.569, respectively), whereas patients in the MPI-low group, experienced a significant increase in MPI score (delta-MPI 0.041, p < 0.001). The evolution of MPI score as a function of LOS had a curvilinear shape because it significantly decreased for patients with short hospitalization (1-6 days) and tended to increase for those with longer LOS. The MPI, a well-established prognostic tool, is sensitive to change of patient's health status and might be used to objectively track and monitor the clinical evolution of acutely ill geriatric patients admitted to the hospital.

A New Computer-Based Tool to Reduce Potentially Inappropriate Prescriptions in Hospitalized Geriatric Patients.

BACKGROUND: Potentially inappropriate prescriptions (PIPs), associated with adverse drug reactions, hospitalization, and wasteful healthcare spending, are common in elderly patients with comorbidities and multiple drugs. OBJECTIVE: Our objective was to develop and validate a new tool to reduce PIPs in a hospitalized geriatric population. METHODS: This was an observational cohort study of two cohorts (development [n = 100 subjects] and validation [n = 449 subjects]) of consecutive patients aged ≥65 years admitted to geriatric wards from April to December 2012. In the development phase, data on clinical and demographic characteristics, Multidimensional Prognostic Index (MPI), and prescribed drugs before hospital admission were collected and processed using a tool that integrates the Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP) criteria and the Micromedex™ Drug-Reax System, a drug-management platform. This tool generated a report that was provided to the treating physicians. The weight of the PIPs, as defined by the Medication Appropriateness Index (MAI), was assessed on admission and on discharge. Similar procedures were followed in the validation cohort. RESULTS: PIPs were independently associated with polypharmacy and with prescribing of antithrombotics, sedatives and antidepressants in both cohorts. The use of the tool led to a significant reduction of the MAI score, both in the development (median score 4 [interquartile range; IQR 1-5] vs. 2 [IQR 0-4], p < 0.001) and in the validation cohorts (median 3 [IQR 1-5] vs. 2 [IQR 0-4], p < 0.001). CONCLUSION: This tool significantly reduced PIPs, as defined by the MAI score, in a hospitalized geriatric population. This strategy might be useful to minimize inappropriate medication exposure in this group.

Measuring pharmacogenetics in special groups: geriatrics.

INTRODUCTION: The cytochrome P450 (CYP) enzymes oxidize about 80% of the most commonly used drugs. Older patients form a very interesting clinical group in which an increased prevalence of adverse drug reactions (ADRs) and therapeutic failures (TFs) is observed. Might CYP drug metabolism change with age, and justify the differences in drug response observed in a geriatric setting? AREAS COVERED: A complete overview of the CYP pharmacogenetics with a focus on the epigenetic CYP gene regulation by DNA methylation in the context of advancing age, in which DNA methylation might change. EXPERT OPINION: Responder phenotypes consist of a continuum spanning from ADRs to TFs, with the best responders at the midpoint. CYP genetics is the basis of this continuum on which environmental and physiological factors act, modeling the phenotype observed in clinical practice. Physiological age-related changes in DNA methylation, the main epigenetic mechanisms regulating gene expression in humans, results in a physiological decrease in CYP gene expression with advancing age. This may be one of the physiological changes that, together with increased drug use, contributed to the higher prevalence of ADRs and TFs observed in the geriatric setting, thus, making geriatrics a special group for pharmacogenetics.

Perspective: the challenge of clinical decision-making for drug treatment in older people. The role of multidimensional assessment and prognosis.

A complex decision path with a careful evaluation of the risk-benefit ratio is mandatory for drug treatment in advanced age. Enrollment biases in randomized clinical trials (RCTs) cause an under-representation of older individuals. In high-risk frail older subjects, the lack of RCTs makes clinical decision-making particularly difficult. Frail individuals are markedly susceptible to adverse drug reactions, and frailty may result in reduced treatment efficacy. Life expectancy should be included in clinical decision-making paths to better assess the benefits and risks of different drug treatments in advanced age. We performed a scoping review of principal hospital- and community-based prognostic indices in older age. Mortality prognostic tools could help clinical decision-making in diagnostics and therapeutics, tailoring appropriate intervention for older patients. The effectiveness of drug treatments may be significantly different in older patients with different risk of mortality. Clinicians need to consider the prognostic information obtained through well-validated, accurate, and calibrated predictive tools to identify those patients who may benefit from drug treatments given with the aim of increasing survival.