Composite kernel machine regression based on likelihood ratio test for joint testing of genetic and gene-environment interaction effect.

Most common human diseases are a result from the combined effect of genes, the environmental factors, and their interactions such that including gene-environment (GE) interactions can improve power in gene mapping studies. The standard strategy is to test the SNPs, one-by-one, using a regression model that includes both the SNP effect and the GE interaction. However, the SNP-by-SNP approach has serious limitations, such as the inability to model epistatic SNP effects, biased estimation, and reduced power. Thus, in this article, we develop a kernel machine regression framework to model the overall genetic effect of a SNP-set, considering the possible GE interaction. Specifically, we use a composite kernel to specify the overall genetic effect via a nonparametric function andwe model additional covariates parametrically within the regression framework. The composite kernel is constructed as a weighted average of two kernels, one corresponding to the genetic main effect and one corresponding to the GE interaction effect. We propose a likelihood ratio test (LRT) and a restricted likelihood ratio test (RLRT) for statistical significance. We derive a Monte Carlo approach for the finite sample distributions of LRT and RLRT statistics. Extensive simulations and real data analysis show that our proposed method has correct type I error and can have higher power than score-based approaches under many situations.

Cognitive impairment, oral self-care function and dental caries severity in community-dwelling older adults.

OBJECTIVE: To investigate whether oral self-care function mediates the associations between cognitive impairment and caries severity in community-dwelling older adults. BACKGROUND: Cognitive impairment affects activities of daily living and compromises oral health, systemic health and quality of life in older adults. However, the associations among cognitive impairment, oral self-care capacity and caries severity remain unclear. This increases difficulty in developing effective interventions for cognitively impaired patients. MATERIALS AND METHODS: Medical, dental, cognitive and functional assessments were abstracted from the dental records of 600 community-dwelling elderly. 230 participants were selected using propensity score matching and categorised into normal, cognitive impairment but no dementia (CIND) and dementia groups based on their cognitive status and a diagnosis of dementia. Multivariable regressions were developed to examine the mediating effect of oral self-care function on the association between cognitive status and number of caries or retained roots. RESULTS: Cognitive impairment, oral self-care function and dental caries severity were intercorrelated. Multivariable analysis showed that without adjusting for oral self-care capacity, cognition was significantly associated with the number of caries or retained roots (p = 0.003). However, the association was not significant when oral self-care capacity was adjusted (p = 0.125). In contrast, individuals with impaired oral self-care capacity had a greater risk of having a caries or retained root (RR = 1.67, 95% CI 1.15, 2.44). CONCLUSION: Oral care capacity mediates the association between cognition and dental caries severity in community-dwelling older adults.

Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

Polycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM) are clonal disorders arising from hematopoietic progenitors. An internet-based protocol was used to collect clinical information and biological specimens from patients with these diseases. High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations. Molecular and cytogenetic analyses demonstrated that homozygous mutations were due to duplication of the mutant allele. JAK2V617F was also identified in granulocyte DNA samples from 37 of 115 ET and 16 of 46 MMM patients, but was not observed in 269 normal individuals. In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase.

Oral health in nursing home residents with different cognitive statuses.

OBJECTIVE: To compare oral health in nursing home (NH) residents with different cognitive statuses. BACKGROUND: Oral health is a significant issue for NH residents because of its relationships to quality of life, systemic health and well-being. It is known that oral health is poor in NH residents. However, how oral health differs in NH residents with different cognitive statuses remains unclear. MATERIALS AND METHODS: Nine hundred and two NH residents were retrospectively recruited from a community-based geriatric dental clinic in Minnesota, USA. Comprehensive medical, dental, cognitive and functional assessments were completed for the participants. On the basis of medical history and cognitive status, participants were categorized into three groups: without cognitive impairment (non-impaired group), with cognitive impairment but no dementia (impaired group) and with dementia (demented group). ANOVA, Chi-square and Fisher's exact tests were used to compare medical, dental and functional statuses between groups. RESULTS: Oral hygiene was poor in NH residents. Forty per cent of participants in the impaired group were edentulous, significantly higher than the edentulism rate in the demented group (29%, p = 0.01). More than 60% of the participants lost 16 or more teeth prior to examination. Depending on their cognitive status, 82-92% of the participants arrived with one or more caries or retained root. Dentate participants in the impaired and demented groups averaged about six caries or retained roots, significantly more than 4.7 caries or retained roots in the non-impaired group (p = 0.01). CONCLUSION: Oral health was poor but slightly different in NH residents with different cognitive and functional statuses.

Vasculitis in a Child With the Hyper-IgM Variant of Ataxia-Telangiectasia.

A subset of patients with Ataxia-Telangiectasia (A-T) have dramatically reduced levels of IgG, IgA, and IgE with retained or elevated IgM levels. Several reports suggest that these A-T patients with a "hyper-IgM phenotype" (HIgM) suffer more clinical immunologic consequences than other A-T patients. The immunopathologic mechanism driving this phenomenon is unknown, making it difficult to predict response to immunomodulatory therapy. We describe an A-T patient with HIgM who underwent tumor necrosis factor (TNF) receptor blockade for cutaneous granuloma and after several months of successful therapy developed non-malignant lymphoproliferation, cytopenia, and increased serum immunoglobulin levels. This process was subsequently followed by an immune-complex-mediated intrarenal small vessel vasculitis that led to renal failure. The vasculitis was successfully treated with rituximab and corticosteroids. This case underscores the importance of HIgM as an unfavorable prognostic indicator in A-T and highlights the complexity of immunomodulatory treatment in this population, and the potential for a successful approach tailored to the immune defect.

Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a Novel AKT1 Fusion-Driven Cancer.

Despite the important role of the PI3K/AKT/mTOR axis in the pathogenesis of cancer, to date there have been few functional oncogenic fusions identified involving the AKT genes. A 12-year-old female with a histopathologically indeterminate epithelioid neoplasm was found to harbor a novel fusion between the LAMTOR1 and AKT1 genes. Through expanded use access, she became the first pediatric patient to be treated with the oral ATP-competitive pan-AKT inhibitor ipatasertib. Treatment resulted in dramatic tumor regression, demonstrating through patient-driven discovery that the fusion resulted in activation of AKT1, was an oncogenic driver, and could be therapeutically targeted with clinical benefit. Post-clinical validation using patient-derived model systems corroborated these findings, confirmed a membrane-bound and constitutively active fusion protein, and identified potential mechanisms of resistance to single-agent treatment with ipatasertib. SIGNIFICANCE: This study describes the patient-driven discovery of the first AKT1 fusion-driven cancer and its treatment with the AKT inhibitor ipatasertib. Patient-derived in vitro and in vivo model systems are used to confirm the LAMTOR1-AKT1 fusion as a tumorigenic driver and identify potential mechanisms of resistance to AKT inhibition.This article is highlighted in the In This Issue feature, p. 565.

Hemoglobin Jamaica plain--a sickling hemoglobin with reduced oxygen affinity.

A baby girl presented with symptomatic sickle cell disease exacerbated by mild hypoxemia, despite a newborn-screening diagnosis of sickle cell trait. DNA sequencing of the beta globin gene revealed that her maternal beta globin allele was normal. Her paternal allele had not only the expected sickle-trait mutation, betaGlu6Val, but also a second, charge-neutral mutation, betaLeu68Phe. Analysis of the patient's hemoglobin revealed that the double-mutant protein, which we called "hemoglobin Jamaica Plain," had severely reduced oxygen affinity. Structural modeling suggested destabilization of the oxy conformation as a molecular mechanism for sickling in a heterozygote at an ambient partial pressure of oxygen.

MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.

BACKGROUND: The JAK2V617F allele has recently been identified in patients with polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis with myeloid metaplasia (MF). Subsequent analysis has shown that constitutive activation of the JAK-STAT signal transduction pathway is an important pathogenetic event in these patients, and that enzymatic inhibition of JAK2V617F may be of therapeutic benefit in this context. However, a significant proportion of patients with ET or MF are JAK2V617F-negative. We hypothesized that activation of the JAK-STAT pathway might also occur as a consequence of activating mutations in certain hematopoietic-specific cytokine receptors, including the erythropoietin receptor (EPOR), the thrombopoietin receptor (MPL), or the granulocyte-colony stimulating factor receptor (GCSFR). METHODS AND FINDINGS: DNA sequence analysis of the exons encoding the transmembrane and juxtamembrane domains of EPOR, MPL, and GCSFR, and comparison with germline DNA derived from buccal swabs, identified a somatic activating mutation in the transmembrane domain of MPL (W515L) in 9% (4/45) of JAKV617F-negative MF. Expression of MPLW515L in 32D, UT7, or Ba/F3 cells conferred cytokine-independent growth and thrombopoietin hypersensitivity, and resulted in constitutive phosphorylation of JAK2, STAT3, STAT5, AKT, and ERK. Furthermore, a small molecule JAK kinase inhibitor inhibited MPLW515L-mediated proliferation and JAK-STAT signaling in vitro. In a murine bone marrow transplant assay, expression of MPLW515L, but not wild-type MPL, resulted in a fully penetrant myeloproliferative disorder characterized by marked thrombocytosis (Plt count 1.9-4.0 x 10(12)/L), marked splenomegaly due to extramedullary hematopoiesis, and increased reticulin fibrosis. CONCLUSIONS: Activation of JAK-STAT signaling via MPLW515L is an important pathogenetic event in patients with JAK2V617F-negative MF. The bone marrow transplant model of MPLW515L-mediated myeloproliferative disorders (MPD) exhibits certain features of human MF, including extramedullary hematopoiesis, splenomegaly, and megakaryocytic proliferation. Further analysis of positive and negative regulators of the JAK-STAT pathway is warranted in JAK2V617F-negative MPD.

Early childhood externalising behaviour problems: child, parenting, and family-related predictors over time.

This study examined the dynamic relationships between child, parenting, and family-related predictor variables and early childhood externalising behaviour problems. A community sample of 395 Australian children was followed longitudinally, and assessed at 4 and 6 years with the Child Behavior Checklist, Teacher Report Form, and standard measures of parenting, temperament, and familial adversity. Variables based on the average scores across the two assessments and the change in scores between assessments were utilised as predictors of parent-reported and teacher-reported externalising behaviour problems at age 6. It was hypothesised that both higher average scores and more detrimental changes in scores, would independently predict externalising problems at age 6. Multivariable analyses found that the presence of parent-reported child externalising problems in six-year-olds were predicted by: (i) the presence of parent-reported child externalising problems at age 4, (ii) higher average "teacher-reported child externalising behaviour," "inflexible temperament," "non-persistent temperament," and "over-reactive parenting," and (iii) an increased "inflexible temperament" score between age 4 and age 6. The presence of teacher-reported child externalising problems at age 6 was predicted by higher average "parent-reported child externalising behaviour," and "over-reactive parenting." The results provide further evidence of the adverse impact of continuing high levels of temperament difficulties and over-reactive parenting on externalising behaviour in early childhood. However, contrary to expectations, the contribution of including the dynamic change scores was limited.

Prediction of resistance to small molecule FLT3 inhibitors: implications for molecularly targeted therapy of acute leukemia.

Mutations in the receptor tyrosine kinase FLT3 occur frequently in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Small molecules that selectively inhibit FLT3 kinase activity induce apoptosis in blasts from AML patients with FLT3 mutations and prolong survival in animal models of FLT3-induced myeloproliferative disease. A spectrum of structurally different small molecules with activity against FLT3 have been described, and their efficacy for treatment of AML and ALL is now being investigated in clinical trials. Here, we describe the results of an in vitro screen designed to identify mutations in the ATP-binding pocket of FLT3 that confer resistance to tyrosine kinase inhibitors. Mutations at four different positions (Ala-627, Asn-676, Phe-691, and Gly-697) were identified that confer varying degrees of resistance to PKC412, SU5614, or K-252a. FLT3 proteins mutated at Ala-627, Asn-676, or Phe-691 remained sensitive to higher concentrations of the inhibitors, but the G697R mutation conferred high-level resistance to each of these inhibitors as well as to six additional experimental inhibitors. These data provide insights into potential mechanisms of acquired resistance of FLT3 to small molecule inhibitors and indicate that the G697R mutation may be a clinically problematic resistance mutation that warrants proactive screening for additional inhibitors.

Usage, adherence and attrition: how new mothers engage with a nurse-moderated web-based intervention to support maternal and infant health. A 9-month observational study.

OBJECTIVES: To identify factors predicting use, adherence and attrition with a nurse-moderated web-based group intervention designed to support mothers of infants aged 0-6 months. DESIGN: 9-Month observational study. SETTING: Community maternal and child health service. PARTICIPANTS: 240 mothers attending initial postnatal health checks at community clinics who were randomly assigned to the intervention arm of a pragmatic preference randomised trial (total randomised controlled trial, n=819; response rate=45%). INTERVENTION: In the first week (phase I), mothers were assisted with their first website login by a research assistant. In weeks 2-7 (phase II), mothers participated in the web-based intervention with an expectation of weekly logins. The web-based intervention was comparable to traditional face-to-face new mothers' groups. During weeks 8-26 (phase III), mothers participated in an extended programme at a frequency of their choosing. PRIMARY OUTCOME MEASURES: Number of logins and posted messages. Standard self-report measures assessed maternal demographic and psychosocial characteristics. RESULTS: In phase II, the median number of logins was 9 logins (IQR=1-25), and in phase III, it was 10 logins (IQR=0-39). Incident risk ratios from multivariable analyses indicated that compared to mothers with the lowest third of logins in phase I, those with the highest third had 6.43 times as many logins in phase II and 7.14 times in phase III. Fifty per cent of mothers logged-in at least once every 30 days for 147 days after phase I and 44% logged-in at least once in the last 30 days of the intervention. Frequency of logins during phase I was a stronger predictor of mothers' level of engagement with the intervention than their demographic and psychosocial characteristics. CONCLUSIONS: Mothers' early use of web-based interventions could be employed to customise engagement protocols to the circumstances of individual mothers with the aim of improving adherence and reducing attrition with web-based interventions. TRIAL REGISTRATION NUMBER: ACTRN12613000204741; Results.

Socio-economic differentials in the health-related quality of life of Australian children: results of a national study.

OBJECTIVE: To examine differences in health-related quality of life (HRQL) of children living in different socio-economic contexts in Australia. METHODS: Parental reports describing the HRQL and socio-economic status of a random national sample of 3,597 school-age children were obtained using the Child Health Questionnaire (CHQ) and a standardised socio-economic interview. Response rate was 70%. RESULTS: Children in families of higher income, whose parents had more years of schooling and were employed and children who lived in two-parent, original families had significantly higher HRQL across a range of domains assessed by the CHQ. CONCLUSION: Children from lower socio-economic backgrounds in Australia have a significantly more negative experience of health and wellness. Such differences may well increase unless deliberate political attention is given to addressing the widening differences in relative wealth in Australia.

Thyroid fine-needle aspiration cytology: performance data of neoplastic and malignant cases as identified from 1558 responses in the ASCP Non-GYN Assessment program thyroid fine-needle performance data.

BACKGROUND: Fine-needle aspiration of the thyroid is a common procedure, with an established role in reducing unnecessary thyroid surgery and identifying neoplasms and malignancies. METHODS: The study evaluated 1558 responses in the American Society for Clinical Pathology (ASCP) Non-GYN Assessment program of aspirates of thyroid neoplasms and malignancies and placed them into the following groups: group A (target or correct interpretation), group B (incorrect interpretation as a benign thyroid nodule), group C (incorrect interpretation malignant aspirate as thyroid neoplasm), and group D (malignant diagnosis with incorrect interpretation). In clinical practice, responses in groups A, C, and D would lead to surgical excision, whereas responses in group B would not. RESULTS: Of a total of 1558 responses, 78.5% of the responses were in group A, 8.5% in group B, 3.75% in group C, and 9.25% in group D. By individual diagnosis, the group rates were 86.5%, 0%, 11%, and 2.5% for anaplastic thyroid carcinoma; 83%, 5.5%, 4.25%, and 7.25% for papillary thyroid carcinoma; 79%, 7%, 6%, and 8% for medullary thyroid carcinoma; 83.5% 6.75%, 0%, and 9.75% for Hürthle cell neoplasm; and 61%, 22%, 0%, and 17% for follicular neoplasm in groups A, B, C, and D respectively. CONCLUSIONS: Fine-needle aspiration was effective in diagnosing thyroid neoplasms and malignancies and in separating thyroid nodules into surgical and nonsurgical categories. Data from a large group of cytology professionals showed good performance; however, there is room for improvement, especially in making specific diagnoses. In particular, follicular neoplasm and follicular variant of papillary thyroid carcinoma were challenging diagnoses for participants.

Assessment of dentally related functional competency for older adults with cognitive impairment--a survey for special-care dental professionals.

This survey was to study whether and how dental professional assess dental-related function in older adults with cognitive impairment (OACI). An invitation was sent to 525 special-care dental professionals, followed by a reminder in 2 weeks. Thirteen percent of the targeted participants completed the survey. Among them, 88% completed a hospital dentistry, geriatric dentistry, or other postgraduate training program. Nearly 70% of the respondents considered somewhat to very difficult to assess dentally related function; 45% did not ever or did not regularly assess dental-related function for OACI. Dental-related functional assessments were often based on a subjective, unstructured approach. Only 6% of the respondents routinely used standard instruments to assess the patients' function. These results indicate that an objective functional assessment based on a standardized instrument has not been routinely incorporated into dental care for OACI, raising concerns for quality of care in this vulnerable population.

Oral health in older adults with dementia living in different environments: a propensity analysis.

This study was to compare oral health in dementia patients living in different environments. One hundred two dementia patients living in the community, assisted living facilities and nursing homes (NH) were retrospectively selected from a community-based dental clinic. Participants' sociodemographics, medical, dental, functional, and cognitive assessment were documented at arrival. Poisson and negative-binomial regressions were developed to assess impacts of residential status on the number of missing teeth and number of caries/retained roots, respectively. Oral health was poor in study participants, regardless of their residential status. Nearly 30% of NH residents were edentulous, about two times higher than those in the community. Dentate participants averaged about 5.9 caries/retained roots at arrival. Forty-four percent of community-dwelling participants and 54% of NH residents presented with five or more caries/retained roots. Holding other factors constant, living environment was not associated with oral health measures, indicating oral health had declined in dementia patients before they were placed into NH.

Dental caries in older adults in the last year of life.

OBJECTIVES: To examine dental caries severity (measured by number of carious teeth) in older adults in the last year of life. DESIGN: Cross-sectional study based on dental records. SETTING: Community-based geriatric dental clinic. PARTICIPANTS: One thousand two hundred sixteen individuals aged 65 and older, including 168 individuals in the last year of life (e.g., individuals died within 1 year after their new-patient examinations). MEASUREMENTS: Information on socioeconomic, medical history, medication, functional status, and oral health measures, including number of carious teeth, was abstracted from dental records. End-of-life status was determined using the National Death Index. Propensities of death were calculated using a logistic regression and then adjusted together with mobility and oral care function in the multivariable regression model to examine the effect of end-of-life status on dental caries. RESULTS: Caries severity differed in end-of-life participants with different oral care function. Of those needing help with oral care, end-of-life participants had only a slightly higher and nonstatistically significant risk (7.5 vs 6.1, adjusted incidence density ratio (IDR) = 1.12, 95% confidence interval (CI) = 0.85-1.48) of having more carious teeth than those not in the last year of life. On the other hand, caries severity was lower in end-of-life participants without impaired oral care function (IDR = 0.53, 95% CI = 0.30-0.92). CONCLUSION: Oral care function modifies the association between caries severity and end-of-life status. Individuals who could maintain oral hygiene independently had a low level of caries at the end of life, however, dental caries had increased before functionally dependent individuals entered their last year of life.

Length of tooth survival in older adults with complex medical, functional and dental backgrounds.

BACKGROUND: Tooth loss can be considered a failure of current oral health care strategies. Knowing how soon this failure will occur can help clinicians enhance preventive strategies for preventing tooth loss and minimizing its impact. The authors conducted a study to detail tooth survival patterns in an older cohort. METHODS: The authors conducted a retrospective longitudinal study of 491 participants aged 43 to 102 years. They treated the participants' dental conditions before they entered the study. They also collected participants' sociodemographic, medical, functional, cognitive and dental data when they first arrived at the clinic. The authors used Fisher exact tests, χ(2) tests and analysis of variance to examine the association between baseline characteristics and tooth survival. They generated Kaplan-Meier estimates and used Cox proportional hazards regression models to detail tooth survival and associated risk factors. RESULTS: The authors found that tooth survival patterns differed among participants who had different numbers of carious teeth or retained roots (carious or broken teeth that were missing most of their coronal structures) when they first arrived at the clinic (P < .001) and between participants who wore removable prostheses and those who did not (P = .02). Participants' tooth loss at different times differed by sex, number of medications being taken and number of carious teeth or retained roots. The authors found that after they adjusted for other factors, tooth survival was associated with the number of carious teeth or retained roots (P = .01), as well as the interaction between the number of carious teeth or retained roots and use of prostheses (P = .02). CONCLUSIONS: Caries and the use of removable prostheses synergistically compromised tooth survival in older patients. Patients who wore prostheses and had multiple active carious teeth or retained roots at arrival had the highest risk of losing teeth soon after their existing conditions were treated. CLINICAL IMPLICATIONS: These findings highlight the need for preventing tooth loss in older adults who wear removable prostheses and have poor oral health. Knowing the groups at the highest risk of experiencing tooth loss soon after dental treatment is received can help dentists better target and design preventive strategies.

Tooth loss patterns in older adults with special needs: a Minnesota cohort.

This study was conducted to detail tooth loss patterns in older adults with special needs. A total of 491 elderly subjects with special needs were retrospectively selected and followed during 10/1999-12/2006. Medical, dental, cognitive, and functional assessments were abstracted from dental records and used to predict risk of tooth loss. Tooth loss events were recorded for subjects during follow-up. Chi-squared tests were used to study the association between tooth loss and the selected risk factors. Logistic, poisson, and negative binomial regressions were developed to study tooth loss patterns. Overall, 27% of the subjects lost at least one tooth during follow-up. Fourteen subjects had tooth loss events per 100 person-years. Tooth loss pattern did not differ significantly among different special-needs subgroups (i.e. community-dwelling vs. long-term care, physically disabled vs. functionally independent). Special-needs subjects with three or more active dental conditions at arrival had more than twice the risk of losing teeth than those without any existing conditions. After adjusting other factors, the number of carious teeth or retained roots at arrival was a significant predictor of tooth loss for older adults with special needs (P = 0.001). These findings indicate that appropriately managing active caries and associated conditions is important to prevent tooth loss for older adults with special needs.

Multidimensional risk assessment for tooth loss in a geriatric population with diverse medical and dental backgrounds.

OBJECTIVES: To introduce a multidimensional approach to assess risk of tooth loss for older adults with diverse medical and dental backgrounds. DESIGN: Retrospective longitudinal study. SETTING: Community-based geriatric dental clinic in Minnesota. PARTICIPANTS: Four hundred ninety-one older adults who presented to the studied clinic as new patients between October 1999 and December 2006, remained dentate after finishing the initial treatment plan, and returned for care at least once thereafter were selected as participants. INTERVENTION: All existing dental conditions were treated before enrollment. Comprehensive dental care was continually provided for all participants during follow-up. MEASUREMENTS: Demographic information, together with medical, dental, functional, and cognitive assessment at arrival, was abstracted from dental records. Logistic, Cox, Poisson, and negative-binomial regressions were developed to assess risk of tooth loss from four dimensions: likelihood of tooth loss, time to first tooth loss, and frequency and rate of tooth loss per person-year. RESULTS: Although the traditional single-dimensional risk assessment approach indicated that number of teeth being carious or retaining roots at arrival was the only contributing factor for tooth loss in older adults, the multidimensional approach found that risk factors of tooth loss differed when assessed from different perspectives. While likelihood of tooth loss and time to first tooth loss were associated only with dental factors, both dental and nondental factors were associated with frequency and rate of tooth loss. CONCLUSION: A single-dimensional risk assessment approach focusing on likelihood of tooth loss alone fails to provide a comprehensive risk profile for older adults. A multidimensional approach should be considered during assessment and treatment planning.