A Multisite Electronic Health Record Integrated Remote Monitoring Intervention for Hypertension Improvement: Protocol for a Randomized Pragmatic Comparative Effectiveness Trial.

BACKGROUND: Hypertension is a major contributor to various adverse health outcomes. Although previous studies have shown the benefits of home blood pressure (BP) monitoring over office-based measurements, there is limited evidence comparing the effectiveness of whether a BP monitor integrated into the electronic health record is superior to a nonintegrated BP monitor. OBJECTIVE: In this paper, we describe the protocol for a pragmatic multisite implementation of a quality improvement initiative directly comparing integrated to nonintegrated BP monitors for hypertension improvement. METHODS: We will conduct a randomized, comparative effectiveness trial at 3 large academic health centers across California. The 3 sites will enroll a total of 660 participants (approximately n=220 per site), with 330 in the integrated BP monitor arm and 330 in the nonintegrated BP control arm. The primary outcome of this study will be the absolute difference in systolic BP in mm Hg from enrollment to 6 months. Secondary outcome measures include binary measures of hypertension (controlled vs uncontrolled), hypertension-related health complications, hospitalizations, and death. The list of possible participants will be generated from a central data warehouse. Randomization will occur after enrollment in the study. Participants will use their assigned BP monitor and join site-specific hypertension interventions. Cross-site learning will occur at regular all-site meetings facilitated by the University of California, Los Angeles Value-Based Care Research Consortium. A pre- and poststudy questionnaire will be conducted to further evaluate participants' perspectives regarding their BP monitor. Linear mixed effects models will be used to compare the primary outcome measure between study arms. Mixed effects logistic regression models will be used to compare secondary outcome measures between study arms. RESULTS: The study will start enrolling participants in the second quarter of 2023 and will be completed by the first half of 2024. Results will be published by the end of 2024. CONCLUSIONS: This pragmatic trial will contribute to the growing field of chronic care management using remote monitoring by answering whether a hypertension intervention coupled with an electronic health record integrated home BP monitor improves patients' hypertension better than a hypertension intervention with a nonintegrated BP monitor. The outcomes of this study may help health system decision makers determine whether to invest in integrated BP monitors for vulnerable patient populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT05390502; clinicaltrials.gov/study/NCT05390502. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45915.

Systems Addressing Frail Elder Care: Description of a Successful Model.

OBJECTIVE: The aim of this article is to describe the Systems Addressing Frail Elder (SAFE) Care model, features of the interprofessional team and reengineered workflow, and details of the intervention. BACKGROUND: Older inpatients are vulnerable to adverse events related to frailty. SAFE Care, an interprofessional team-based program, was developed and evaluated in a cluster randomized controlled trial (C-RCT). Results found reduced length of stay and complications. The purpose of this article is to support and encourage the replication of this innovation or to help facilitate implementation of a similar process of organizational change. METHODS: This was a review of model features and intervention data abstracted from electronic health records. RESULTS: Salient features of team composition, training, and workflow are presented. The C-RCT intention-to-treat sample included 792 patients, of whom 307 received the SAFE Care huddle intervention. The most frequent problem was mobility (85.7%), and most frequent recommendation was fall precautions protocol (83.1%). CONCLUSIONS: The SAFE Care model may provide a standardized framework to approach, assess, and address the risks of hospitalized older adults.

Identification and team-based interprofessional management of hospitalized vulnerable older adults.

BACKGROUND: Extended hospital stays and complications are common among older adults and may lead to morbidity and loss of independence. Specialized geriatric units have been shown to improve outcomes but, with the growing numbers of older adults, may be difficult to scale to meet needs. PURPOSE: The purpose was to evaluate a quality improvement initiative that redesigned unit-based workflow and trained interprofessional teams on general medical/surgical units to create care plans for vulnerable older adults using principles of comprehensive geriatric assessment and team management. METHOD: The evaluation included a cluster randomized controlled trial of 10 medical/surgical units and intention-to-treat analysis of all patients meeting risk screening criteria. RESULTS: N = 1,384, median age = 80.9 years, and 53.5% female. Mean difference in observed vs. expected length of stay was 1.03 days shorter (p = .006); incidence of complications (odds ratio [OR] = 0.45; 95% confidence interval [CI] = 0.21-0.98) and transfer to intensive care (OR = 0.45; 95% CI = 0.25-0.79) lower among patients admitted to intervention units; incidence of discharge to institutional care was higher (OR = 1.43; 95% CI = 1.06-1.93). Mortality during hospitalization (OR = 0.64; 95% CI = 0.37-1.11) did not differ between groups. CONCLUSION: Reorganizing general medical/surgical units to provide team-based interprofessional care can improve outcomes among hospitalized older adults.

Validating SPICES as a Screening Tool for Frailty Risks among Hospitalized Older Adults.

Older patients are vulnerable to adverse hospital events related to frailty. SPICES, a common screening protocol to identify risk factors in older patients, alerts nurses to initiate care plans to reduce the probability of patient harm. However, there is little published validating the association between SPICES and measures of frailty and adverse outcomes. This paper used data from a prospective cohort study on frailty among 174 older adult inpatients to validate SPICES. Almost all patients met one or more SPICES criteria. The sum of SPICES was significantly correlated with age and other well-validated assessments for vulnerability, comorbid conditions, and depression. Individuals meeting two or more SPICES criteria had a risk of adverse hospital events three times greater than individuals with either no or one criterion. Results suggest that as a screening tool used within 24 hours of admission, SPICES is both valid and predictive of adverse events.

Early recognition of risk factors for adverse outcomes during hospitalization among Medicare patients: a prospective cohort study.

BACKGROUND: There is a persistently high incidence of adverse events during hospitalization among Medicare beneficiaries. Attributes of vulnerability are prevalent, readily apparent, and therefore potentially useful for recognizing those at greatest risk for hospital adverse events who may benefit most from preventive measures. We sought to identify patient characteristics associated with adverse events that are present early in a hospital stay. METHODS: An interprofessional panel selected characteristics thought to confer risk of hospital adverse events and measurable within the setting of acute illness. A convenience sample of 214 Medicare beneficiaries admitted to a large, academic medical center were included in a quality improvement project to develop risk assessment protocols. The data were subsequently analyzed as a prospective cohort study to test the association of risk factors, assessed within 24 hours of hospital admission, with falls, hospital-acquired pressure ulcers (HAPU) and infections (HAI), adverse drug reactions (ADE) and 30-day readmissions. RESULTS: Mean age = 75(±13.4) years. Risk factors with highest prevalence included >4 active comorbidities (73.8%), polypharmacy (51.7%), and anemia (48.1%). One or more adverse hospital outcomes occurred in 46 patients (21.5%); 56 patients (26.2%) were readmitted within 30 days. Cluster analysis described three adverse outcomes: 30-day readmission, and two groups of in-hospital outcomes. Distinct regression models were identified: Weight loss (OR = 3.83; 95% CI = 1.46, 10.08) and potentially inappropriate medications (OR = 3.05; 95% CI = 1.19, 7.83) were associated with falls, HAPU, procedural complications, or transfer to intensive care; cognitive impairment (OR = 2.32; 95% CI = 1.24, 4.37), anemia (OR = 1.87; 95% CI = 1.00, 3.51) and weight loss (OR = 2.89; 95% CI = 1.38, 6.07) were associated with HAI, ADE, or length of stay >7 days; hyponatremia (OR = 3.49; 95% CI = 1.30, 9.35), prior hospitalization within 30 days (OR = 2.66; 95% CI = 1.31, 5.43) and functional impairment (OR = 2.05; 95% CI = 1.02, 4.13) were associated with 30-day readmission. CONCLUSIONS: Patient characteristics recognizable within 24 hours of admission can be used to identify increased risk for adverse events and 30-day readmission.

Development, reliability, and validity of a new Preference and Satisfaction Questionnaire.

OBJECTIVES: Existing questionnaires that assess preference and/or satisfaction with postmenopausal bone loss treatments were reviewed and determined to be inadequate for the assessment of an oral pill versus a subcutaneous injection. The Preference and Satisfaction Questionnaire (PSQ) was developed to assess preference, satisfaction, and bother with a weekly oral tablet versus a once every 6 months subcutaneous injection for treatment of postmenopausal bone loss. METHODS: Questions were developed based on literature review and expert input. Content validity of the PSQ in this patient population was assessed among current or previous bisphosphonate users in group interviews, and item comprehension and readability were also evaluated. Reliability, validity, and structure of the questionnaire were assessed in two phase 3 randomized clinical trials. RESULTS: Twenty-four women participated in cognitive interviews and found the PSQ understandable and acceptable. Subsequently, 1583 trial participants took the PSQ. Interitem correlations, ranging from 0.50 to 0.97 for preference items, 0.85 to 0.94 for pill-satisfaction items, and 0.84 to 0.92 for injection-satisfaction items, and a well-fitting confirmatory factor analysis (root mean square error of approximation 0.04, nonnormed fit index 0.99, and root mean square residual 0.08) supported the structure of the instrument. Cronbach's alpha reliability values for pill satisfaction, injection satisfaction, pill bother, and injection bother were 0.93, 0.89, 0.82, and 0.61, respectively. Discriminative validity was indicated with better satisfaction and bother scores being related to adherence and the absence of adverse events. CONCLUSIONS: The PSQ is a valid and reliable measure and may be a valuable tool to assess patient preference and satisfaction with a weekly oral tablet and 6-month subcutaneous injection for postmenopausal bone loss.

Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder: a meta-analysis.

OBJECTIVE: To systematically review evidence of the treatment benefits of selective serotonin reuptake inhibitors (SSRIs) for symptoms related to severe premenstrual syndrome (PMS) and premenstrual dysphoric disorder. DATA SOURCES: We conducted electronic database searches of MEDLINE, Web of Science, Cochrane Library, Embase, PsycINFO, and Cinahl through March 2007, and hand-searched reference lists and pertinent journals. METHODS OF STUDY SELECTION: Studies included in the review were double-blind, randomized, controlled trials comparing an SSRI with placebo that reported a change in a validated score of premenstrual symptomatology. Studies had to report follow-up for any duration longer than one menstrual cycle among premenopausal women who met clinical diagnostic criteria for PMS or premenstrual dysphoric disorder. From 2,132 citations identified, we pooled results from 29 studies (in 19 citations) using random-effects meta-analyses and present results as odds ratios (ORs). TABULATION, INTEGRATION, AND RESULTS: Our meta- analysis, which included 2,964 women, demonstrates that SSRIs are effective for treating PMS and premenstrual dysphoric disorder (OR 0.40, 95% confidence interval [CI] 0.31-0.51). Intermittent dosing regimens were found to be less effective (OR 0.55, 95% CI 0.45-0.68) than continuous dosing regimens (OR 0.28, 95% CI 0.18-0.42). No SSRI was demonstrably better than another. The choice of outcome measurement instrument was associated with effect size estimates. The overall effect size is smaller than reported previously. CONCLUSION: Selective serotonin reuptake inhibitors were found to be effective in treating premenstrual symptoms, with continuous dosing regimens favored for effectiveness.

Differences in symptom scores and health outcomes in premenstrual syndrome.

BACKGROUND: In studies of premenstrual syndrome (PMS), a significant response to treatment is commonly defined as a 50% reduction in symptom scores, but empirical support for this definition is lacking. We compared healthcare utilization in women with and without PMS according to the Daily Record of Severity of Problems (DRSP) scores in order to determine the degree of symptomatic variation in premenstrual symptoms associated with differences in the burden of illness. METHODS: Participants were women aged 18-45 years enrolled in a medical group in southern California. Respondents completed the Medical Outcomes Study Short Form-36 (SF-36) at baseline and the DRSP symptom and occupational productivity items daily. Luteal phase DRSP scores were averaged over two consecutive cycles. Respondents were categorized as having mild/no and moderate/severe PMS or premenstrual dysphoric disorder (PMDD) using a previously published, validated algorithm. Medical costs were estimated from medical claims data over the 2 years prior to study entry. RESULTS: Compared with women with moderate/severe PMS/PMDD (n = 117), those with mild/no PMS/PMDD (n = 271) had 43% lower DRSP scores (29.7 and 52.4, p < 0.05), higher SF-36 mental component summary (49.9 and 40.5, p < 0.0001) and physical component summary (52.6 and 50.8, p = 0.04) scores, and fewer workdays per month with reduced productivity (13.3 and 22.0, p < 0.0001) and workdays missed due to health reasons (1.2 and 2.7, p = 0.001). Women with moderate/severe PMS/PMDD had greater odds of having >10 office visits (OR = 1.80, 95% CI 1.01, 3.22) and of accumulating >$500 in medical charges (OR = 1.9, 95% CI 1.2, 3.0). CONCLUSIONS: A 43% difference in premenstrual vs. postmenstrual symptom scores is associated with a significant difference in healthcare burden. These data support the use of a 50% reduction in symptom ratings as a clinically relevant improvement in PMS/PMDD treatment trials, although smaller differences may also be meaningful.

Using the daily record of severity of problems as a screening instrument for premenstrual syndrome.

OBJECTIVE: To assess symptom ratings on the first day of menses to identify women at high risk of clinically significant premenstrual syndrome (PMS) who should undergo further evaluation. METHODS: A cohort of 697 women kept daily symptom ratings using the Daily Record of Severity of Problems (DRSP). The DRSP includes 21 symptom items grouped within 11 domains. DRSP scores on the first day of menses were calculated using the sum of all 21 items (standard method), the sum of the highest rated items within each domain (alternative method), and the sum of seven items derived from modeling. Seventy percent of the study sample was randomly assigned into a model-building set to identify optimal cutoff scores for PMS screening. The remaining 30% comprised a testing set used to compare PMS screening results to a PMS diagnosis based on two cycles of daily DRSP ratings. RESULTS: Of the initial study sample, 388 participants (55.7%) completed two cycles of daily ratings. The prevalence of PMS was 30.4%. In the model-building set, the positive and negative predictive values of the 21-item DRSP scores were 53.8% and 83.4% using the standard method and 52.7% and 84.0% using the alternative method. Corresponding values were 55.0% and 84.9% for an abbreviated seven-item DRSP version. These results were confirmed in the testing set. CONCLUSION: The DRSP administered on the first day of menses is an acceptable screening instrument to identify women who may have PMS.

Evaluating the criteria used for identification of PMS.

OBJECTIVE: Criteria for defining premenstrual syndrome (PMS) were assessed by comparing a reference definition previously demonstrated to be associated with reduced health-related quality of life and impaired productivity with alternative definitions based on criteria stringency variations. METHODS: Health-related quality of life data were collected from the Medical Outcomes Study Short Form-36 (SF-36) for women aged 18-64 years. Women maintained daily calendars of emotional and physical symptoms and work productivity. PMS prevalence and differences in health-related quality of life and work productivity between women with and without PMS were compared using alternative definitions. RESULTS: Across criteria, PMS prevalence ranged from 19% to 30%. Regardless of the criteria used, PMS was associated with reductions in health-related quality of life, with Mental Components Subscale scores 5-12 points lower for women with PMS compared to those without PMS. Likewise, across definitions, women with PMS had greater work productivity impairment than women without PMS, netting 4 additional days with reduced productivity per month. CONCLUSIONS: PMS prevalence varies based on criteria used to define illness. However, PMS is associated with reductions in health-related quality of life and work productivity impairment regardless of the criteria used.

Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis.

OBJECTIVE: There is a rapidly evolving debate on the indications and appropriate duration of therapy for postmenopausal hormone therapy. The objective of this meta-analysis was to examine the specific relationships of postmenopausal estrogen therapy (ET), postmenopausal combined (estrogen-progestogen) hormone therapy (CHT), and the incidence of breast cancer. DESIGN: We performed computerized searches of MEDLINE and CancerLit through September 2003 and reviewed reference lists of retrieved studies and meta-analyses. We included English-language studies that identified noncontraceptive postmenopausal hormone use; reported on the risks of "current use" of ET and/or CHT and breast cancer incidence; were case-control, cohort, or experimental; and reported either an odds ratio (OR), relative risk (RR), or HR with CIs. Two investigators were involved during all stages of study selection and independently extracted all data selected for inclusion in meta-analyses. RESULTS: Meta-analysis of 13 studies of ET and breast cancer (700,000 women) resulted in an OR of 1.16 (95% confidence limits [CL] 1.06, 1.28), with estimates for less than 5 years use 1.16 (1.02, 1.32) and more than 5 years use 1.20 (1.06, 1.37). Meta-analysis of eight studies of CHT and breast cancer (650,000 women) resulted in an OR of 1.39 (95% CL 1.12, 1.72), with estimates for less than 5 years use 1.35 (1.16, 1.57) and more than 5 years use 1.63 (1.22, 2.18). CONCLUSIONS: Data from observational studies support the association of increased but considerably different risks for breast cancer incidence among current users of ET and CHT. These represent the first pooled estimates for ET. CHT estimates correspond to those from randomized trials.

Estimating direct and indirect costs of premenstrual syndrome.

OBJECTIVE: To quantify the economic impact of premenstrual syndrome (PMS) on the employer. METHODS: Data were collected from 374 women aged 18-45 with regular menses. Direct costs were quantified using administrative claims of these patients and the Medicare Fee Schedule. Indirect costs were quantified by both self-reported days of work missed and lost productivity at work. Regression analyses were used to develop a model to project PMS-related direct and indirect costs. RESULTS: A total of 29.6% (n = 111) of the participants were diagnosed with PMS. A PMS diagnosis was associated with an average annual increase of $59 in direct costs (P < 0.026) and $4333 in indirect costs per patient (P < 0.0001) compared with patients without PMS. CONCLUSIONS: A PMS diagnosis correlated with a modest increase in direct medical costs and a large increase in indirect costs.

The association between quality improvement activities performed by managed care organizations and quality of care.

PURPOSE: Little data are available to assess the efforts of managed care organizations to improve quality of care. This analysis assessed differences in performance rates between organizations with and without quality improvement activities. METHODS: We reviewed 399 self-reported quality improvement activities submitted by organizations seeking accreditation by the National Committee for Quality Assurance. Processes or outcomes assessed in quality improvement activities were linked to corresponding measures in the effectiveness-of-care database of the Health Plan Employer Data and Information Set (HEDIS). Performance rates for managed care organizations with and without quality improvement activities were then compared. RESULTS: The cross-sectional analysis included 79 quality improvement activities from 50 organizations, covering 12 effectiveness-of-care categories. Each activity had a matching performance score in the database. Financial incentives for providers were associated with substantially higher performance rates in organizations employing this type of intervention. Eight effectiveness-of-care categories had at least four organizations reporting specific quality improvement activities for the care category of interest; statistically significant improvements were observed for follow-up visits for patients after hospitalization for mental illness, checkups after delivery, and screening for cervical cancer. CONCLUSION: Based on objective and audited information, the estimated effects of self-reported quality improvement activities were often small and inconsistent. In some instances, the observed effect was contrary to the expected direction. Limitations of the available dataset and the caveats of a cross-sectional study design precluded a number of analytical options. Longer-term, prospective studies are needed to explore further the relation between quality improvement activities and objective measures of clinical performance.

A prospective assessment investigating the relationship between work productivity and impairment with premenstrual syndrome.

Our objective was to assess life domain and work-related impairment in patients experiencing premenstrual syndrome (PMS). A sample of women, 18 to 45 years of age, completed the Daily Rating of Severity of Problems Form to record daily symptoms for two consecutive menstrual cycles. In the workplace, women with PMS reported higher absenteeism rates (2.5 days vs. 1.3 days; P = 0.006) and more workdays with 50% or less of typical productivity per month (7.2 days vs. 4.2 days; P < 0.0001). Women with PMS in one of two menstrual cycles reported a greater number of days with impairment in routine work, school, and household activities in comparison with women without PMS. Results indicate that PMS leads to substantial im in normal daily activities and occupational productivity and significantly increased work absenteeism.

Can change in high-density lipoprotein cholesterol levels reduce cardiovascular risk?

BACKGROUND: The cardiovascular risk reduction observed in many trials of lipid-lowering agents is greater than expected on the basis of observed low-density lipoprotein cholesterol (LDL-C) level reductions. Our objective was to explore the degree to which high-density lipoprotein cholesterol (HDL-C) level changes explain cardiovascular risk reduction. METHODS: A systematic review identified trials of lipid-lowering agents reporting changes in HDL-C and LDL-C levels and the incidence of coronary heart disease (CHD). The observed relative risk reduction (RRR) in CHD morbidity and mortality rates was calculated. The expected RRR, given the treatment effect on total cholesterol level, was calculated for each trial with logistic regression coefficients from observational studies. The difference between observed and expected RRR was plotted against the change in HDL-C level, and a least-squares regression line was calculated. RESULTS: Fifty-one trials were identified. Nineteen statin trials addressed the association of HDL-C with CHD. Limited numbers of trials of other therapies precluded additional analyses. Among statin trials, therapy reduced total cholesterol levels as much as 32% and LDL-C levels as much as 45%. HDL-C level increases were <10%. Treatment effect on HDL-C levels was not a significant linear predictor of the difference in observed and expected CHD mortality rates, although we observed a trend in this direction (P =.08). Similarly, HDL-C effect was not a significant linear predictor of the difference between observed and expected RRRs for CHD morbidity (P =.20). CONCLUSIONS: Although a linear trend toward greater risk reduction was observed with greater effects on HDL-C, differences were not statistically significant. The narrow range of HDL-C level increases in the statin trials likely reduced our ability to detect a beneficial HDL-C effect, if present.

Health and economic impact of the premenstrual syndrome.

OBJECTIVE: To explore the effect of the premenstrual syndrome (PMS) on health-related quality of life, health care utilization and occupational functioning. STUDY DESIGN: A cross-sectional cohort study of women prospectively diagnosed with PMS. RESULTS: Among women completing the survey, 28.7% were diagnosed with PMS. Women with PMS had significantly lower scores on the Mental Component Summary (MCS) and Physical Component Summary (PCS) scale scores of the Medical Outcomes Study Short Form-36 as compared to women without PMS (MCS = 42.8 vs. 49.5, P < .001, and PCS = 51.1 vs. 53.0, P = .04). Women with PMS reported reduced work productivity, interference with hobbies and greater number of work days missed for health reasons (P < .001). In addition, women with PMS experienced an increased frequency of ambulatory health care provider visits (P = .04) and were more likely to accrue > $500 in visit costs over 2 years (P < .006). CONCLUSION: Findings from this study suggest that premenstrual symptoms significantly affect health-related quality of life and may result in increased health care utilization and decreased occupational productivity.

The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD).

Currently it is estimated that 3-8% of women of reproductive age meet strict criteria for premenstrual dysphoric disorder (PMDD). Assessment of published reports demonstrate that the prevalence of clinically relevant dysphoric premenstrual disorder is probably higher. 13-18% of women of reproductive age may have premenstrual dysphoric symptoms severe enough to induce impairment and distress, though the number of symptoms may not meet the arbitrary count of 5 symptoms on the PMDD list. The impairment and lowered quality of life for PMDD is similar to that of dysthymic disorder and is not much lower than major depressive disorder. Nevertheless, PMS/PMDD is still under-recognized in large published epidemiological studies, as well as assessments of burden of disease. It is demonstrated here that the burden of PMS/PMDD as well as the disability adjusted life years (DALY) lost due to this repeated-cyclic disorder is in the same magnitude as major recognized disorders. Appropriate recognition of the disorder and its impact should lead to treatment of more women with PMS/PMDD. Efficacious treatments are available. They should reduce individual suffering and impact on family, society, and economy.

The cost-effectiveness of irbesartan in the treatment of hypertensive patients with type 2 diabetic nephropathy.

BACKGROUND: End-stage renal disease (ESRD)-related health care costs are substantial. Improving clinical outcomes in patients at risk of progression to ESRD could lead to considerable health care savings. OBJECTIVE: We estimated the cost-effectiveness of irbesartan compared with placebo or amlodipine in the treatment of patients with type 2 diabetes mellitus, hypertension, and overt nephropathy. METHODS: Three treatments for hypertension patients with type 2 diabetes mellitus and nephropathy were assessed: (1) irbesartan, (2) amlodipine, and (3) placebo. A Markov model was developed based on primary data from the Irbesartan in Diabetic Nephropathy Trial and the United States Renal Data System. Projected survival and costs were compared for each treatment at 3-, 10-, and 25-year time horizons. Different assumptions of treatment benefits and costs were tested with use of sensitivity analyses. RESULTS: At 10 and 25 years, the model projected irbesartan to be both the least costly and most effective (ie, demonstrating a survival advantage) strategy. At 25