Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Optimal adaptive sequential designs for crossover bioequivalence studies.

In prior works, this group demonstrated the feasibility of valid adaptive sequential designs for crossover bioequivalence studies. In this paper, we extend the prior work to optimize adaptive sequential designs over a range of geometric mean test/reference ratios (GMRs) of 70-143% within each of two ranges of intra-subject coefficient of variation (10-30% and 30-55%). These designs also introduce a futility decision for stopping the study after the first stage if there is sufficiently low likelihood of meeting bioequivalence criteria if the second stage were completed, as well as an upper limit on total study size. The optimized designs exhibited substantially improved performance characteristics over our previous adaptive sequential designs. Even though the optimized designs avoided undue inflation of type I error and maintained power at ≥ 80%, their average sample sizes were similar to or less than those of conventional single stage designs.

Delivery Characteristics, Acceptability, and Depression Outcomes of a Home-based Depression Intervention for Older African Americans: The Get Busy Get Better Program.

PURPOSE OF THE STUDY: To facilitate replication, we examined delivery characteristics, acceptability, and depression outcomes of a home-based intervention, Get Busy Get Better, Helping Older Adults Beat the Blues (GBGB). GBGB, previously tested in a randomized trial, reduced depressive symptoms and enhanced quality of life in African Americans. DESIGN AND METHODS: A total of 208 African Americans aged above 55 years with Patient Health Questionnaire (PHQ-9) scores ≥5 on two subsequent screenings were randomized to receive GBGB immediately or 4 months later. GBGB involves up to 10 home sessions consisting of care management, referral/linkage, depression education/symptom recognition, stress reduction, and behavioral activation. Interventionists recorded delivery characteristics (dose, intensity) and perceived acceptability of sessions. Baseline and post-tests were used to characterize participants and examine associations between dose/intensity and depression scores. Participant satisfaction and perceived benefits were examined at 8 months. RESULTS: Of 208 participants, 181 (87%, mean age = 69.6) had treatment data. Of these, 165 (91.2%) had ≥3 treatment sessions (minimal dose). Participants had on average 8.1 sessions (SD = 2.6) for an average of 65.4min (SD = 18.3) each. Behavioral activation and care management were provided the most (average of six sessions for average duration = 17.9 and 22.2min per session respectively), although all participants received each treatment component. GBGB was perceived as highly acceptable and beneficial by interventionists and participants. More sessions and time in program were associated with greater symptom reduction. IMPLICATIONS: GBGB treatment components were highly acceptable to participants. Future implementation and sustainability challenges include staffing, training requirements, reimbursement limitations, competing agency programmatic priorities, and generalizability to other groups.

Role of public standards in the safety and efficacy of biologic medicines.

In this report, we emphasize the importance of public monographs with reference materials, coupled with careful process and change control and attention to GMPs, as a means of advancing access to good quality, safe, and effective medicines, with emphasis on available and incoming biologic medicines. With adequate control of articles covered by a monograph, these public standards can form the basis for a global public quality platform that covers reference products, non-interchangeable reference products, biosimilars, and interchangeable biosimilars. Working collaboratively with all stakeholders, new approaches allow these public standards to emerge nationally and globally in a timely way. Yet, there are increasing limitations in the availability of public standards for biologic medicines, which may reverse many decades of progress. Solutions are considered in this report.

Caregiver's perceptions of the relationship of pain to behavioral and psychiatric symptoms in older community-residing adults with dementia.

OBJECTIVES: Pain is underrecognized and undermanaged in older adults with dementia. Because dementia patients have a diminished capacity to communicate discomfort, untreated pain may be expressed in the form of behavioral and psychiatric symptoms. The goal of the present study was to examine the relationship between pain and behavioral and psychiatric symptoms of dementia in community-residing older adults from the perspective of the family caregiver. MATERIALS AND METHODS: Dyads composed of 272 dementia patients, and their family caregivers were assessed to determine dementia patient's mental status; family caregiver's assessment of care recipient's pain, functional dependence, and number of behavioral symptoms; analgesic use; and demographic information. RESULTS: Hierarchical multiple regression analysis controlling for age, marital status, race, functional disability, and analgesic use showed that pain explained a small but significant percent of variance in the number of behavioral symptoms (3%, P<0.001). Pain had a stronger influence on the number of behavioral and psychiatric symptoms of dementia among those with severe cognitive impairment (F1,69=11.75, P<0.001) compared with those with low to moderate cognitive impairment (F1,199=4.543, P=0.034.). DISCUSSION: The findings indicate that pain is a risk factor for behavioral symptoms in individuals with dementia and suggest that pain is a more significant predictor of behavior for individuals with severe dementia, compared with those with mild/moderate stage dementia. These results reinforce the importance of proper pain assessment and its management as part of dementia care planning.

Correlates of quality of life for individuals with dementia living at home: the role of home environment, caregiver, and patient-related characteristics.

OBJECTIVES: To examine prevalence of modifiable risk factors and their contribution to patient quality of life (QoL) as rated by dementia patients and family caregivers. DESIGN: Cross-sectional. SETTING: Home environment. PARTICIPANTS: 88 patients and their caregivers. MEASUREMENTS: Modifiable characteristics of home environments, patients, and caregivers were observed or obtained through interview. Demographics and ratings of patients' QoL were obtained from patients and caregivers. RESULTS: Patients had mean Mini-mental Status Examination (MMSE) score = 17.7 ± 4.6, (range: 10-28) on an average 7.7 ± 2.4 neuropsychiatric behaviors, 6.0 ± 3.1 health conditions and moderate functional challenges; 70.7% (N = 58) had fall risk; 60.5% (N = 52) had sleep problems at least once weekly; and 42.5% (N = 37) had pain. An average of 8.1 ± 5.2 home hazards and 5.4 ± 4.1 adaptations were observed; 51.7% had unmet device/navigation needs. Patients' and caregivers' QoL ratings were unrelated to MMSE; and patients' self-rated QoL was higher than rated by caregivers. Number of health conditions and unmet device/navigation needs were inversely associated with patient self-rated QoL, and number of health conditions, frequency of behaviors, and level of negative communications were inversely associated with caregiver's assessment of patient QoL. Positive endorsement of caregiving was positively associated with caregiver's appraisal of patient QoL. Other factors were unrelated. CONCLUSIONS: Most patients lived at home with high fall risk, unmanaged behavioral symptoms, pain, sleep disturbances, environmental challenges, and multiple hazards. Except for health, factors associated with lower QoL differed for patients and caregivers. Results suggest need to improve QoL by addressing modifiable risk factors and tailoring interventions to patient and caregiver perspectives.

A home-based intervention to reduce depressive symptoms and improve quality of life in older African Americans: a randomized trial.

BACKGROUND: Effective care models for treating older African Americans with depressive symptoms are needed. OBJECTIVE: To determine whether a home-based intervention alleviates depressive symptoms and improves quality of life in older African Americans. DESIGN: Parallel, randomized trial stratified by recruitment site. Interviewers assessing outcomes were blinded to treatment assignment. (ClinicalTrials.gov: NCT00511680). SETTING: A senior center and participants' homes from 2008 to 2010. PATIENTS: African Americans aged 55 years or older with depressive symptoms. INTERVENTION: A multicomponent, home-based intervention delivered by social workers or a wait-list control group that received the intervention at 4 months. MEASUREMENTS: Self-reported depression severity at 4 months (primary outcome) and depression knowledge, quality of life, behavioral activation, anxiety, function, and remission at 4 and 8 months. RESULTS: Of 208 participants (106 and 102 in the intervention and wait-list groups, respectively), 182 (89 and 93, respectively) completed 4 months and 160 (79 and 81, respectively) completed 8 months. At 4 months, participants in the intervention group showed reduced depression severity (difference in mean change in Patient Health Questionnaire-9 score from baseline, -2.9 [95% CI, -4.6 to -1.2]; difference in mean change in Center for Epidemiologic Studies Depression Scale score from baseline, -3.7 [CI, -5.4 to -2.1]); improved depression knowledge, quality of life, behavioral activation, and anxiety (P < 0.001); and improved function (P = 0.014) compared with wait-list participants. More intervention than wait-list participants entered remission at 4 months (43.8% vs. 26.9%). After treatment, control participants showed benefits similar in magnitude to those of participants in the initial intervention group. Those in the initial intervention group maintained benefits at 8 months. LIMITATION: The study had a small sample, short duration, and differential withdrawal rate. CONCLUSION: A home-based intervention delivered by social workers could reduce depressive symptoms and enhance quality of life in most older African Americans. PRIMARY FUNDING SOURCE: National Institute of Mental Health.

Phenotypic parameters predict time to normalization in infants with hypogammaglobulinemia.

PURPOSE: Infants with recurrent infection may be found to have hypogammaglobulinemia without impaired specific antibody responses. Many will be diagnosed with transient hypogammaglobulinemia of infancy. METHODS: This study used a parametric survival analysis of 100 infants with hypogammaglobulinemia to predict time to normalization. RESULTS: Aggregate initial immunoglobulins (IgG + IgA + IgM), as a percentage of age-adjusted normal, predicted time to resolution: median time to resolution for the infants in the lowest quartile of aggregate levels (≤81 % of age-adjusted lower limits) was greater than 5 years, with 34 % resolving in 3 years. For infants in the highest quartile (≥130 % of age-adjusted lower limits), the median was 9.9 months, with 77 % resolving in 3 years (P = 0.008). Initial IgG level, as a percentage of age-adjusted normal, also predicted resolution: the median time in the lowest quartile (≤78 % of age-adjusted lower limits) was greater than 5 years, with 36 % resolving in 3 years. In the highest quartile (≥128 %), the median time was 14.5 months, with 70 % resolving in 3 years (P = 0.010). Male sex was associated with more rapid resolution. The median time in males was 13 months, with 73 % resolution in 3 years. The median time in females was greater than 5 years, with 32 % resolution in 3 years. CONCLUSIONS: These results suggest that if a term infant presents with hypogammaglobulinemia, protective specific antibody titers, and an absence of other known immune deficiency, initial immunoglobulin levels and sex may predict time to normalization.

Identification of and beliefs about depressive symptoms and preferred treatment approaches among community-living older African Americans.

OBJECTIVE: To examine older African American's recognition of and beliefs about depressive symptoms, preferred symptom management strategies, and factors associated with willingness to use mental health treatments. Differences between the depressed and nondepressed and men and women were examined. DESIGN: Cross-sectional survey. SETTING: Home, senior center. PARTICIPANTS: A total of 153 senior center members (56 male, 97 female) 55 years and older. MEASUREMENTS: Using a depression vignette, participants indicated if the person was depressed and their endorsement of items reflecting beliefs, stigma, symptom management, and willingness to use treatments (yes/no). A 9-item Patient Health Questionnaire assessed current symptomatology. RESULTS: Overall, 24.2% reported depressive symptoms (≥5); 88.2% correctly identified the person in the vignette as depressed. Most (≥75%) endorsed active symptom management strategies, preference for treatment in physician and therapist offices, and willingness to take medications, seek therapy, see doctor, and attend support groups; less than 33% viewed depression as stigmatizing, whereas 48% viewed depression as normal aging. Logistic regressions revealed lower education, higher physical function, and feeling okay if community knew of depression diagnosis were associated with willingness to see physician if feeling depressed; being married and believing antidepressant medications are beneficial were related to willingness to use medications. Different associations emerged for depressed/nondepressed and men and women. CONCLUSIONS: Overall, this older African American sample had positive attitudes and beliefs and endorsed traditional treatment modalities suggesting that beliefs alone are unlikely barriers to underutilization of mental health services. Because different factors were associated with willingness to seek physician help and use medications and factors differed for depressed/nondepressed and by sex, interventions should be tailored.

Toward global standards for comparator pharmaceutical products: case studies of amoxicillin, metronidazole, and zidovudine in the Americas.

This study compared in vitro dissolution characteristics and other quality measures of different amoxicillin, metronidazole, and zidovudine products purchased in the Americas to a comparator pharmaceutical product (CPP). These three drugs are classified as Biopharmaceutics Classification System Class I drugs with the possibility that dissolution findings might be used to document bioequivalence. All investigated zidovudine products were found to be in vitro equivalent to the CPP. Only 3 of 12 tested amoxicillin products were found to be in vitro equivalent to the CPP. None of the tested metronidazole products were in vitro equivalent to the CPP. These findings suggest but do not confirm bioinequivalence where in vitro comparisons failed, given that an in vivo blood level study might have confirmed bioequivalence. At times, identifying a CPP in one of the selected markets proved difficult. The study demonstrates that products sold across national markets may not be bioequivalent. When coupled with the challenge of identifying a CPP in different countries, the results of this study suggest the value of an international CPP as well as increased use of BCS approaches as means of either documenting bioequivalence or signaling the need for further in vivo studies. Because of increased movement of medicines across national borders, practitioners and patients would benefit from these approaches.

Two-stage hierarchical modeling for analysis of subpopulations in conditional distributions.

In this work, we develop modeling and estimation approach for the analysis of cross-sectional clustered data with multimodal conditional distributions where the main interest is in analysis of subpopulations. It is proposed to model such data in a hierarchical model with conditional distributions viewed as finite mixtures of normal components. With a large number of observations in the lowest level clusters, a two-stage estimation approach is used. In the first stage, the normal mixture parameters in each lowest level cluster are estimated using robust methods. Robust alternatives to the maximum likelihood estimation are used to provide stable results even for data with conditional distributions such that their components may not quite meet normality assumptions. Then the lowest level cluster-specific means and standard deviations are modeled in a mixed effects model in the second stage. A small simulation study was conducted to compare performance of finite normal mixture population parameter estimates based on robust and maximum likelihood estimation in stage 1. The proposed modeling approach is illustrated through the analysis of mice tendon fibril diameters data. Analyses results address genotype differences between corresponding components in the mixtures and demonstrate advantages of robust estimation in stage 1.

Primary and secondary reference materials for procedures to test the quality of medicines and foods.

At present a complex global patchwork of private and public monographs and reference materials is variously available to help ensure the quality of medicines and foods. The relationship of these monographs and reference materials, one to another, frequently is inconsistently understood and documented.This article considers the complexity of monographs and reference materials with a focus on qualifying one reference material relative to another.

Additional results for 'Sequential design approaches for bioequivalence studies with crossover designs'.

In 2008, this group published a paper on approaches for two-stage crossover bioequivalence (BE) studies that allowed for the reestimation of the second-stage sample size based on the variance estimated from the first-stage results. The sequential methods considered used an assumed GMR of 0.95 as part of the method for determining power and sample size. This note adds results for an assumed GMR = 0.90. Two of the methods recommended for GMR = 0.95 in the earlier paper have some unacceptable increases in Type I error rate when the GMR is changed to 0.90. If a sponsor wants to assume 0.90 for the GMR, Method D is recommended. Copyright © 2011 John Wiley & Sons, Ltd.

Development of a performance verification test for USP apparatus 4.

PURPOSE: To evaluate salicylic acid tablets as a candidate reference material in a Performance Verification Test (PVT) when a USP performance test for dissolution (General Chapter <711>) relies on USP Apparatus 4 (flow-through cell). METHODS: We developed a dissolution procedure relying on Apparatus 4 and salicylic acid tablets. Thereafter, a designed experiment was conducted to identify operational variables that significantly affect salicylic acid dissolution in this apparatus. RESULTS: Four variables (size of glass beads, cell temperature, flow rate, level of deaeration) and one combination effect (deaeration/bead size) were significant for mean percent dissolved. Two variables (tablet orientation, level of deaeration) were significant for standard deviation results, but these effects were less pronounced than those for mean percent dissolved results. Three variables (analyst, tester manufacturer, amount of glass beads) had no statistically significant effects on either the mean or standard deviation of the responses. CONCLUSIONS: The proposed PVT is capable of probing effects of changes in several critical operational parameters of Apparatus 4. Salicylic acid tablets were shown to be a suitable reference material for the PVT. The PVT using salicylic acid tablets satisfies important aspects of a PVT.

Establishing new acceptance limits for dissolution performance verification of USPC apparatus 1 and 2 using USPC prednisone tablets reference standard.

PURPOSE: On 1 March 2010, the US Pharmacopeial Convention released into commerce Lot P1I300 of its Prednisone Tablets Reference Standard for use in periodic performance verification testing (PVT) of dissolution Apparatus 1 and 2. This report presents the collaborative study data, development of the acceptance limits, and results from supporting work for this Lot. METHODS: The collaborative study involved 25 collaborators who provided data for Apparatus 1 and 31 who provided data for Apparatus 2. These limits are for the geometric mean and percent coefficient of variation (%CV) instead of per-individual results as for prior lots. Stability of results and sensitivity to test performance parameters were also studied. RESULTS: To determine new PVT acceptance limits, the authors calculated geometric mean and variance components as percent coefficient of variation. The move to the geometric mean and %CV criteria brings the acceptance criteria in line with current accepted statistics and provides a more realistic assessment of the system's performance. Results for Apparatus 1 are stable over time, but for Apparatus 2, the mean decreases over time. Acceptance criteria are adjusted for this trend. Lot P1 demonstrates sensitivity to test performance parameters (vessels and degassing). CONCLUSIONS: Apparatus 1 results are stable over time. Those in Apparatus 2 show a decrease over time in the geometric mean but show no trend in variability. The current tablets are shown to remain sensitive to two operational parameters, degassing and vessel dimensions, not covered by mechanical calibration. The new acceptance limits for Lot P1 are based on geometric mean and %CV for Prednisone Tablets Reference Standard Lot P1I300. The limits better control variability than the prior per-individual-result limits.

A biobehavioral home-based intervention and the well-being of patients with dementia and their caregivers: the COPE randomized trial.

CONTEXT: Optimal treatment to postpone functional decline in patients with dementia is not established. OBJECTIVE: To test a nonpharmacologic intervention realigning environmental demands with patient capabilities. DESIGN, SETTING, AND PARTICIPANTS: Prospective 2-group randomized trial (Care of Persons with Dementia in their Environments [COPE]) involving patients with dementia and family caregivers (community-living dyads) recruited from March 2006 through June 2008 in Pennsylvania. INTERVENTIONS: Up to 12 home or telephone contacts over 4 months by health professionals who assessed patient capabilities and deficits; obtained blood and urine samples; and trained families in home safety, simplifying tasks, and stress reduction. Control group caregivers received 3 telephone calls and educational materials. MAIN OUTCOME MEASURES: Functional dependence, quality of life, frequency of agitated behaviors, and engagement for patients and well-being, confidence using activities, and perceived benefits for caregivers at 4 months. RESULTS: Of 284 dyads screened, 270 (95%) were eligible and 237 (88%) randomized. Data were collected from 209 dyads (88%) at 4 months and 173 (73%) at 9 months. At 4 months, compared with controls, COPE patients had less functional dependence (adjusted mean difference, 0.24; 95% CI, 0.03-0.44; P = .02; Cohen d = 0.21) and less dependence in instrumental activities of daily living (adjusted mean difference, 0.32; 95% CI, 0.09-0.55; P = .007; Cohen d = 0.43), measured by a 15-item scale modeled after the Functional Independence Measure; COPE patients also had improved engagement (adjusted mean difference, 0.12; 95% CI, 0.07-0.22; P = .03; Cohen d = 0.26), measured by a 5-item scale. COPE caregivers improved in their well-being (adjusted mean difference in Perceived Change Index, 0.22; 95% CI, 0.08-0.36; P = .002; Cohen d = 0.30) and confidence using activities (adjusted mean difference, 0.81; 95% CI, 0.30-1.32; P = .002; Cohen d = 0.54), measured by a 5-item scale. By 4 months, 64 COPE dyads (62.7%) vs 48 control group dyads (44.9%) eliminated 1 or more caregiver-identified problems (chi(2/1) = 6.72, P = . 01). CONCLUSION: Among community-living dyads, a nonpharmacologic biobehavioral environmental intervention compared with control resulted in better outcomes for COPE dyads at 4 months. Although no group differences were observed at 9 months for patients, COPE caregivers perceived greater benefits. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00259454.

Targeting and managing behavioral symptoms in individuals with dementia: a randomized trial of a nonpharmacological intervention.

OBJECTIVES: To test the effects of an intervention that helps families manage distressing behaviors in family members with dementia. DESIGN: Two-group randomized trial. SETTING: In home. PARTICIPANTS: Two hundred seventy-two caregivers and people with dementia. INTERVENTION: Up to 11 home and telephone contacts over 16 weeks by health professionals who identified potential triggers of patient behaviors, including communication and environmental factors and patient undiagnosed medical conditions (by obtaining blood and urine samples) and trained caregivers in strategies to modify triggers and reduce their upset. Between 16 and 24 weeks, three telephone contacts reinforced strategy use. MEASUREMENTS: Primary outcomes were frequency of targeted problem behavior and caregiver upset with and confidence managing it at 16 weeks. Secondary outcomes were caregiver well-being and management skills at 16 and 24 weeks and caregiver perceived benefits. Prevalence of medical conditions for intervention patients were also examined. RESULTS: At 16 weeks, 67.5% of intervention caregivers reported improvement in targeted problem behavior, compared with 45.8% of caregivers in a no-treatment control group (P=.002), and reduced upset with (P=.03) and enhanced confidence managing (P=.01) the behavior. Additionally, intervention caregivers reported less upset with all problem behaviors (P=.001), less negative communication (P=.02), less burden (P=.05), and better well-being (P=.001) than controls. Fewer intervention caregivers had depressive symptoms (53.0%) than control group caregivers (67.8%, P=.02). Similar caregiver outcomes occurred at 24 weeks. Intervention caregivers perceived more study benefits (P<.05), including ability to keep family members home, than controls. Blood and urine samples of intervention patients with dementia showed that 40 (34.1%) had undiagnosed illnesses requiring physician follow-up. CONCLUSION: Targeting behaviors upsetting to caregivers and modifying potential triggers improves symptomatology in people with dementia and caregiver well-being and skills.

Measurement science for food and drug monographs: toward a global system.

This article continues USP's public dialogs about applications of modern measurement science (metrology) to public or private specifications (monographs) of food and drug articles. An objective of the discussion is to promote understanding of traceability and uncertainty of measurement results. Adoption of modern metrologic principles helps ensure that a measurement of one or more property values (attributes) of a food or drug article are acceptable without regard to when (time), where (space), or how (technology) the measurement was conducted. The approach is applicable to both in-process and end-product measurements and facilitates and supports understanding of manufacturing and measurement variability relative to acceptance criteria. Application of modern metrologic principles to measurement of food and drug articles expands opportunities to ensure availability of good quality food and drugs in national and international markets.

Long-term effect on mortality of a home intervention that reduces functional difficulties in older adults: results from a randomized trial.

OBJECTIVES: To evaluate the long-term mortality effect of a home-based intervention previously shown to reduce functional difficulties and whether survivorship benefits differ according to initial mortality risk level. DESIGN: Two-group randomized trial with survivorship followed up to 4 years from study entry. SETTING: Homes of urban community-living elderly people. PARTICIPANTS: Three hundred nineteen adults aged 70 and older with difficulties performing daily activities. INTERVENTION: Occupational and physical therapy sessions to instruct participants in compensatory strategies, home modifications, home safety, fall recovery techniques, and balance and muscle strength exercises. MEASUREMENTS: Survival time was number of days between baseline interview and date of death, as determined using data from the National Death Index or December 31, 2005. Participants were stratified according to baseline mortality risk (low, moderate, high) using a prognostic indicator. RESULTS: At 2 years, intervention participants (n=160) had a 5.6% mortality rate (n=9 deaths) and controls (n=159) a 13.2% rate (n=21 deaths; P=.02). Mortality rates remained lower for intervention participants up to 3.5 years from study entry. At 2 years, intervention participants with moderate mortality risk had a 16.7% mortality rate (n=16 deaths/96), compared with 28.2% for equivalent control group participants (n=24 deaths/85; P=.02). By 3 years, mortality rates were not statistically significantly different between the experimental and control groups. CONCLUSIONS: The intervention extended survivorship up to 3.5 years and maintained statistically significant differences for 2 years. Subjects at moderate mortality risk derived the most intervention benefit. Findings suggest that the intervention could be a low-cost clinical tool to delay functional decline and mortality.

Change in criteria for USP dissolution performance verification tests.

The US Pharmacopeial Convention has been evaluating its performance verification tests (PVT) for several years. These tests help ensure the integrity of the US Pharmacopeia performance test when a dissolution procedure, as described in General Chapter Dissolution <711>, is relied upon to test a nonsolution orally administered dosage form. One result of the evaluation is a change in the PVT criterion from one based on individual tablet results to one based on the mean and variability of a set of tablets. This paper describes the new PVT and its criterion and how its acceptance limits are derived from results of a collaborative study, explains a two-stage option for the test, and presents operating characteristics.